Development of Targeted siRNA Nanocomplexes to Prevent Fibrosis in Experimental Glaucoma Filtration Surgery.

RNAi induced by double-stranded small interfering RNA (siRNA) molecules has attracted great attention as a naturally occurring approach to silence gene expression with high specificity. The myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway is a master regulator of cytoskeletal gene expression and, thus, represents a promising target to prevent fibrosis. A major hurdle to implementing siRNA therapies is the method of delivery, and we have, thus, optimized lipid-peptide-siRNA (LPR) nanoparticles containing MRTF-B siRNAs as a targeted approach to prevent conjunctival fibrosis. We tested 15 LPR nanoparticle formulations with different lipid compositions, surface charges, and targeting or non-targeting peptides in human conjunctival fibroblasts. In vitro, the LPR formulation of the DOTMA/DOPE lipid with the targeting peptide Y (LYR) was the most efficient in MRTF-B gene silencing and non-cytotoxic compared to the non-targeting formulation. In vivo, subconjunctival administration of LYR nanoparticles containing MRTF-B siRNAs doubled bleb survival in a pre-clinical rabbit model of glaucoma filtration surgery. Furthermore, MRTF-B LYR nanoparticles reduced the MRTF-B mRNA by 29.6% in rabbit conjunctival tissues, which led to significantly decreased conjunctival scarring with no adverse side effects. LYR-mediated delivery of siRNA shows promising results to increase bleb survival and to prevent conjunctival fibrosis after glaucoma filtration surgery.

Social media-based civic engagement solutions for dengue prevention in Sri Lanka: results of receptivity assessment.

This article focuses on a novel social media-based system that addresses dengue prevention through an integration of three components: predictive surveillance, civic engagement and health education. The aim was to conduct a potential receptivity assessment of this system among smartphone users in the city of Colombo, the epicenter of the dengue epidemic in the island country of Sri Lanka. Grounded in Protection Motivation Theory (PMT) and using a convenience sampling approach, the cross-sectional survey assessed perceived severity (PSe), perceived susceptibility (PSu), perceived response efficacy (PRE), perceived self-efficacy (PSE) and intention-to-use (IU) among 513 individuals. The overall receptivity to the system was high with a score of >4.00 on a five-point scale. Participants belonging to younger, better educated and higher income groups reported significantly better perceptions of the efficaciousness of the system, were confident in their ability to use the system, and planned to use it in the future. PMT variables contributed significantly to regression models predicting IU. We concluded that a social media-based system for dengue prevention will be positively received among Colombo residents and a targeted, strategic health communication effort to raise dengue-related threat perceptions will be needed to encourage greater adoption and use of the system.

A Social Media mHealth Solution to Address the Needs of Dengue Prevention and Management in Sri Lanka.

BACKGROUND: Sri Lanka has witnessed a series of dengue epidemics over the past five years, with the western province, home to the political capital of Colombo, bearing more than half of the dengue burden. Existing dengue monitoring prevention programs are exhausted as public health inspectors (PHIs) cope with increasing workloads and paper-based modes of surveillance and education, characterizing a reactive system unable to cope with the enormity of the problem. On the other hand, the unprecedented proliferation and affordability of mobile phones since 2009 and a supportive political climate have thus far remained unexploited for the use of mobile-based interventions for dengue management. OBJECTIVE: To conduct a needs assessment of PHIs in Colombo with respect to their dengue-related tasks and develop a new mobile-based system to address these needs while strengthening existing systems. METHODS: One-on-one in-depth interviews were conducted with 29 PHIs to a) gain a nuanced, in-depth understanding of the current state of surveillance practices, b) understand the logistical, technological and social challenges they confront, and c) identify opportunities for mobile-based interventions. Quantitative analysis included simple descriptive statistics while qualitative analysis comprised textual analysis of 209 pages of transcripts (or nearly 600 minutes of conversations) using grounded theory approaches. RESULTS: Current paper-based data collection practices for dengue surveillance involved a circuitous, time consuming process that could take between 7-10 days to officially report and record a single case. PHIs confronted challenges in terms of unreliable, standalone GIS devices, delays in registering mosquito breeding sites and lack of engagement from communities while delivering dengue education. These findings, in concert with a high motivation to use mobile-based systems, informed the development of Mo-Buzz, a mobile-based system that integrates three components - digitized surveillance, dynamic disease mapping and digitized dengue education - on a common platform. The system was developed through an iterative, evolutionary, collaborative process, consistent with the Spiral model of software development and is currently being used by all 55 PHIs in the CMC system. CONCLUSIONS: Given the entrenched nature of existing paper-based systems in PHIs' work habits, we expect a gradual adoption curve for Mo-Buzz in the future. Equally, we expect variable adoption of the system with respect to its specific components, and specific PHI sub-groups (younger versus older). The Mo-Buzz intervention is a response to multiple calls by the global mHealth community for collaborations in the area of mobile interventions for global health. Our experience revealed that the benefits of this paradigm lies in alleviating country-specific public health challenges through a commonly shared understanding of cultural mores, and sharing of knowledge and technologies. We call upon future researchers to further dissect the applicability of the Spiral Model of software development to mHealth interventions and contribute to the mHealth evidence debate from theoretical and applied perspectives.

Baseline Evaluation of a Participatory Mobile Health Intervention for Dengue Prevention in Sri Lanka.

Challenges posed by infectious disease outbreaks have led to a range of participatory mobile phone-based innovations that use the power of crowdsourcing for disease surveillance. However, the dynamics of participatory behavior by crowds in such interventions have yet to be examined. This article reports results from a baseline evaluation of one such intervention called Mo-Buzz, a mobile-based crowdsource-driven socially mediated system developed to address gaps in dengue surveillance and education in Colombo, Sri Lanka. We conducted a 30-minute cross-sectional field survey (N = 404) among potential users of Mo-Buzz in Colombo. We examined individual, institutional, and cultural factors that influence their potential intention-to-use Mo-Buzz and assessed if these factors varied by demographic factors. Descriptive analysis revealed high perceived ease-of-use (PEOU; M = 3.81, SD = 0.44), perceived usefulness (PU; M = 4.01, SD = 0.48), and intention-to-use (PI; M = 3.91, SD = 0.46) among participants. Analysis of variance suggested participants in the 31 to 40 years age group reported highest PEOU, whereas the oldest group reported high perceived institutional efficacy (M = 3.59, SD = 0.64) and collectivistic tendencies. Significant differences (at the p < .05 level) were also found by education and income. Regression analysis demonstrated that PU, behavioral control, institutional efficacy, and collectivism were significant predictors of PI. We concluded that despite high overall PI, future adoption and use of Mo-Buzz will be shaped by a complex mix of factors at different levels of the public health ecology. Implications of study findings from theoretical and practical perspectives related to the future adoption of mobile-based participatory systems in public health are discussed and ideas for a future research agenda presented.

A 21st century approach to tackling dengue: Crowdsourced surveillance, predictive mapping and tailored communication.

This paper describes a social media system to prevent dengue in Sri Lanka and potentially in the rest of the South and Southeast Asia regions. The system integrates three concepts of public health prevention that have thus far been implemented only in silos. First, the predictive surveillance component uses a computer simulation to forewarn health authorities and the general public about impending disease outbreaks. The civic engagement component allows the general public to use social media tools to interact and engage with health authorities by aiding them in surveillance efforts by reporting symptoms, mosquito bites and breeding sites using smartphone technologies. The health communication component utilizes citizen data gathered from the first two components to disseminate customized health awareness messages to enhance knowledge and increase preventive behaviors among citizens. The system, known as "Mo-Buzz," will be made available on a host of digital platforms like simple mobile phones, smart phones and a website. We present challenges and lessons learnt including content validation, stakeholder collaborations and applied trans-disciplinary research.