Human-Based Immune Responsive In Vitro Infection Models for Validation of Novel TLR4 Antagonists Identified by Computational Discovery.

Infectious diseases are still a major problem worldwide. This includes microbial infections, with a constant increase in resistance to the current anti-infectives employed. Toll-like receptors (TLRs) perform a fundamental role in pathogen recognition and activation of the innate immune response. Promising new approaches to combat infections and inflammatory diseases involve modulation of the host immune system via TLR4. TLR4 and its co-receptors MD2 and CD14 are required for immune response to fungal and bacterial infection by recognition of microbial cell wall components, making it a prime target for drug development. To evaluate the efficacy of anti-infective compounds early on, we have developed a series of human-based immune responsive infection models, including immune responsive 3D-skin infection models for modeling fungal infections. By using computational methods: pharmacophore modeling and molecular docking, we identified a set of 46 potential modulators of TLR4, which were screened in several tests systems of increasing complexity, including immune responsive 3D-skin infection models. We could show a strong suppression of cytokine and chemokine response induced by lipopolysacharide (LPS) and Candida albicans for individual compounds. The development of human-based immune responsive assays provides a more accurate and reliable basis for development of new anti-inflammatory or immune-modulating drugs.

Correction: Evaluating the Feasibility and Acceptability of a Mobile Health-Based Female Community Health Volunteer Program for Hypertension Control in Rural Nepal: Cross-Sectional Study.

[This corrects the article DOI: 10.2196/15419.].

Evaluating the Feasibility and Acceptability of a Mobile Health-Based Female Community Health Volunteer Program for Hypertension Control in Rural Nepal: Cross-Sectional Study.

BACKGROUND: Hypertension is a major modifiable risk factor for cardiovascular disease, the world's leading cause of death. The prevalence of hypertension is disproportionately higher in South Asian countries than in other regions of the world. Screening for hypertension in primary care settings remains a challenge in many South Asian countries, including Nepal. Nepal is located in the Himalayan Mountains region, posing significant geographical challenges for its rural citizens to access primary health care and service delivery. This barrier increases the costs and inconvenience for rural Nepalis to access hypertension screening and treatment. As a result, the prevalence of hypertension in Nepal tripled in the last 25 years to 22.4%-38.6%. Nepal's Ministry of Health and Population relies on female community health volunteers to link health centers and communities to provide basic health services. Over 50,000 of these volunteers in Nepal have received basic health care training and are assigned to take care of maternal and child health. Due to limited health care resources, adopting new methods to control hypertension is an urgent need in Nepal. Several recent studies in Nepal have recommended extending the role of female community health volunteers to include hypertension management through blood pressure monitoring and home-based education. OBJECTIVE: The goal of this study was to assess if a mobile health-based female community health volunteer approach of combining the traditional community health volunteer program with digital technologies would be feasible and acceptable in rural Nepal. METHODS: In this study, we recruited 17 female community health volunteers and extended their role from maternal and child health to hypertension management through screening blood pressures. RESULTS: All 17 female community health volunteers successfully measured 1113 rural Nepalis' blood pressures, identified 169 hypertensive patients, and collected health behaviors data of the 169 hypertensive patients. Among the 169 patients, 70% of them had a mobile phone, and 92% were interested in receiving health-related information via a mobile phone. Among those who were interested in receiving information via a mobile phone, 84% preferred voice calls, and 7% and 1% preferred texting and apps, respectively. CONCLUSIONS: Results from this study indicate that a digital health intervention that leverages feature-phones combined with female community health volunteers may be an acceptable and pragmatic way to implement an evidence-based program to reduce hypertension in rural Nepal.