In Silico Identification of Potential Natural Product Inhibitors of Human Proteases Key to SARS-CoV-2 Infection.

Presently, there are no approved drugs or vaccines to treat COVID-19, which has spread to over 200 countries and at the time of writing was responsible for over 650,000 deaths worldwide. Recent studies have shown that two human proteases, TMPRSS2 and cathepsin L, play a key role in host cell entry of SARS-CoV-2. Importantly, inhibitors of these proteases were shown to block SARS-CoV-2 infection. Here, we perform virtual screening of 14,011 phytochemicals produced by Indian medicinal plants to identify natural product inhibitors of TMPRSS2 and cathepsin L. AutoDock Vina was used to perform molecular docking of phytochemicals against TMPRSS2 and cathepsin L. Potential phytochemical inhibitors were filtered by comparing their docked binding energies with those of known inhibitors of TMPRSS2 and cathepsin L. Further, the ligand binding site residues and non-covalent interactions between protein and ligand were used as an additional filter to identify phytochemical inhibitors that either bind to or form interactions with residues important for the specificity of the target proteases. This led to the identification of 96 inhibitors of TMPRSS2 and 9 inhibitors of cathepsin L among phytochemicals of Indian medicinal plants. Further, we have performed molecular dynamics (MD) simulations to analyze the stability of the protein-ligand complexes for the three top inhibitors of TMPRSS2 namely, qingdainone, edgeworoside C and adlumidine, and of cathepsin L namely, ararobinol, (+)-oxoturkiyenine and 3α,17α-cinchophylline. Interestingly, several herbal sources of identified phytochemical inhibitors have antiviral or anti-inflammatory use in traditional medicine. Further in vitro and in vivo testing is needed before clinical trials of the promising phytochemical inhibitors identified here.

InSpire to Promote Lung Assessment in Youth: Evolving the Self-Management Paradigms of Young People With Asthma.

BACKGROUND: Asthma is the most common chronic disease in childhood, disproportionately affecting urban, minority, and disadvantaged children. Individualized care plans supported by daily lung-function monitoring can reduce morbidity and mortality. However, despite 20 years of interventions to increase adherence, only 50% of US youth accurately follow their care plans, which leads to millions of preventable hospitalizations, emergency room visits, and sick days every year. We present a feasibility study of a novel, user-centered approach to increasing young people's lung-function monitoring and asthma self-care. Promoting Lung Assessment in Youth (PLAY) helps young people become active managers of their asthma through the Web 2.0 principles of participation, cocreation, and information sharing. Specifically, PLAY combines an inexpensive, portable spirometer with the motivational power and convenience of mobile phones and virtual-community gaming. OBJECTIVE: The objective of this study was to develop and pilot test InSpire, a fully functional interface between a handheld spirometer and an interactive game and individualized asthma-care instant-messaging system housed on a mobile phone. METHODS: InSpire is an application for mobile smartphones that creates a compelling world in which youth collaborate with their physicians on managing their asthma. Drawing from design-theory on global timer mechanics and role playing, we incentivized completing spirometry maneuvers by making them an engaging part of a game young people would want to play. The data can be sent wirelessly to health specialists and return care recommendations to patients in real-time. By making it portable and similar to applications normally desired by the target demographic, InSpire is able to seamlessly incorporate asthma management into their lifestyle. RESULTS: We describe the development process of building and testing the InSpire prototype. To our knowledge, the prototype is a first-of-its kind mobile one-stop shop for asthma management. Feasibility testing in children aged 7 to 14 with asthma assessed likability of the graphical user interface as well as young people's interest in our incentivizing system. Nearly 100% of children surveyed said they would play games like those in PLAY if they involved breathing into a spirometer. Two-thirds said they would prefer PLAY over the spirometer alone, whereas 1/3 would prefer having both. No children said they would prefer the spirometer over PLAY. CONCLUSIONS: Previous efforts at home-monitoring of asthma in children have experienced rapid decline in adherence. An inexpensive monitoring technology combined with the computation, interactive communication, and display ability of a mobile phone is a promising approach to sustainable adherence to lung-function monitoring and care plans. An exciting game that redefines the way youth conduct health management by inviting them to collaborate in their health better can be an incentive and a catalyst for more far-reaching goals.

A novel handheld device for use in remote patient monitoring of heart failure patients--design and preliminary validation on healthy subjects.

Remote patient monitoring (RPM) holds great promise for reducing the burden of congestive heart failure (CHF). Improved sensor technology and effective predictive algorithms can anticipate sudden decompensation events. Enhanced telemonitoring systems would promote patient independence and facilitate communication between patients and their physicians. We report the development of a novel hand-held device, called Blue Box, capable of collecting and wirelessly transmitting key cardiac parameters derived from three integrated biosensors: 2 lead electrocardiogram (ECG), photoplethysmography and bioelectrical impedance (bioimpedance). Blue Box measurements include time intervals between consecutive ECG R-waves (RR interval), time duration of the ECG complex formed by the Q, R and S waves (QRS duration), bioimpedance, heart rate and systolic time intervals. In this study, we recruited 24 healthy subjects to collect several parameters measured by Blue Box and assess their value in correlating with cardiac output measured with Echo-Doppler. Linear correlation between the heart rate measured with Blue Box and cardiac output from Echo-Doppler had a group average correlation coefficient of 0.80. We found that systolic time intervals did not improve the model significantly. However, STIs did inversely correlate with increasing workloads.

Assessing the acceptability and usability of an interactive serious game in aiding treatment decisions for patients with localized prostate cancer.

BACKGROUND: Men diagnosed with localized prostate cancer face a potentially life-altering treatment decision that can be overwhelming. Enhancing patient knowledge through education can significantly reduce feelings of uncertainty while simultaneously increasing confidence in decision making. Serious games have been shown in other populations to increase health knowledge and assist with the health decision-making process. We developed an interactive serious game, Time After Time, which translates evidence-based treatment outcome data into an accessible and understandable format that men can utilize in their prostate cancer treatment decision-making process. The game specifically aims to raise men's awareness and understanding of the impact of health-related quality of life issues associated with the major treatment options and to enrich their conversations with their health care providers. OBJECTIVE: This study determined the acceptability and usability of the alpha version of Time After Time, an interactive decision aid for men diagnosed with localized prostate cancer, in order to inform future iterations of the serious game. METHODS: The study employed a mixed methods approach to assess the acceptability and usability of the Time After Time serious game using qualitative focus groups and a quantitative Likert scale survey. RESULTS: A total of 13 men who had already completed treatment for localized prostate cancer completed the survey and participated in focus group meetings. The majority of the study participants rated Time After Time as an appropriate decision tool for localized prostate cancer and verified that it meets its goals of increasing focus on side effects and generating questions for the patient's health care team. However, participants also expressed concerns about game usability and the diversity of information covered regarding treatment options and potential treatment outcomes. CONCLUSIONS: Serious games are a promising approach to health education and decision support for older men. Participants were receptive to the idea of a serious game as a decision aid in localized prostate cancer. However, usability issues are a major concern for this demographic, as is clarity and transparency of data sources.

Effect of font size, italics, and colour count on web usability.

Web usability measures the ease of use of a website. This study attempts to find the effect of three factors - font size, italics, and colour count - on web usability. The study was performed using a set of tasks and developing a survey questionnaire. We performed the study using a set of human subjects, selected from the undergraduate students taking courses in psychology. The data computed from the tasks and survey questionnaire were statistically analysed to find if there was any effect of font size, italics, and colour count on the three web usability dimensions. We found that for the student population considered, there was no significant effect of font size on usability. However, the manipulation of italics and colour count did influence some aspects of usability. The subjects performed better for pages with no italics and high italics compared to moderate italics. The subjects rated the pages that contained only one colour higher than the web pages with four or six colours. This research will help web developers better understand the effect of font size, italics, and colour count on web usability in general, and for young adults, in particular.