Delivering therapeutics to mucosal tissues such as the nasal and gastrointestinal tracts, is highly desirable due to ease of access and dense vasculature. However, the mucus layer effectively captures and removes most therapeutic macromolecules and devices. In previous work, we have shown that nanoengineered microparticles (NEMPs) adhere through the mucus layer, exhibiting up to 1000 times the pull-off force of an unmodified microsphere, and showing greater adhesion than some chemical targeting means. In this paper, we demonstrate that nanotopography improves device adhesion in vivo, increasing retention time up to ten-fold over unmodified devices. Moreover, we observe considerable adhesion in several cell lines using an in vitro shear flow model, indicating that this approach is promising for numerous tissues. We then demonstrate that nanowire-mediated adhesion is highly robust to variation in nanowire surface charge and cellular structure and function, and we characterize particle loading and elution. We present a form of cytoadhesion that utilizes the physical interaction of nanoengineered surfaces with subcellular structures to produce a robust and versatile cytoadhesive for drug delivery. These nanoscale adhesive mechanisms are also relevant to fields such as tissue engineering and wound healing because they likely affect stem cell differentiation, cell remodeling, migration, etc.
The integrity of the p53 tumor suppressor pathway is compromised in the majority of cancers. In 7% of cancers, p53 is inactivated by abnormally high levels of MDM2—an E3 ubiquitin ligase that polyubiquitinates p53, marking it for degradation. MDM2 engages p53 through its hydrophobic cleft and blockage of that cleft by small molecules can re-establish p53 activity. Small molecule MDM2 inhibitors have been developed, but there is likely to be a high cost and long time period before effective drugs reach the market. An alternative is to repurpose FDA-approved drugs. This report describes a new approach, called Computational Conformer Selection, to screen for compounds that potentially inhibit MDM2. This screen was used to computationally generate up to 600 conformers of 3,244 FDA-approved drugs. Drug conformer similarities to 41 computationally-generated conformers of MDM2 inhibitor nutlin 3a were ranked by shape and charge distribution. Quantification of similarities by Tanimoto combo scoring resulted in scores that ranged from 0.142 to 0.802. In silico docking of drugs to MDM2 was used to calculate binding energies and to visualize contacts between the top-ranking drugs and the MDM2 hydrophobic cleft. We present 15 FDA-approved drugs predicted to inhibit p53/MDM2 interaction.
W e describe a novel nanostructured target plate for laser desorption/ionization (LDI) mass spectrometry, NALDI (Bruker Daltonics, Billerica, MA) target plates. The active surface comprises several layers of inorganic materials that are structured at the nanoscale and then further coated with a hydrophobic organic layer that facilitates sample deposition and LDI performance. These targets have been designed to analyze low mass (below 1500 Da), relatively polar, organic molecules and they have been shown to be up to 10 times more sensitive at detecting analytes in this range than conventional Matrix-assisted laser desorption/ionizationd Time of Flight (MALDI)-TOF analysis. The targets can be used on standard LDI-TOF mass spectrometers and have been designed to fit the Bruker Flex series of mass spectrometers. This study demonstrates the utility of these targets for analyzing pharmaceutical compounds and demonstrates their superiority over conventional MALDI both in terms of performance and ease of use. Finally, we also demonstrate that these targets can be used in a unique sample preparation and analysis mode by allowing the capture and analysis of analytes from complex biological solutions.
Background During the COVID-19 pandemic, the Ministry of Health asked Singapore’s private general practitioners (GPs) to perform swab testing in their clinics, but some GPs had concerns about swabber protection. Our aim was to develop a swabbing booth to address these concerns. Methods We developed a prototype with potential GP users using a human-centred design approach and piloted it with 10 GP clinics. The pilot was then extended to 170 GP clinics around Singapore. These GPs were then surveyed on user satisfaction. Results Ninety-three GPs (54%) responded. The majority (75%) practiced in public residential estates in small practices (mean 1.95 doctors). 86% requested the booth to enhance swabber protection. 74% “would recommend” or “would strongly recommend” the booth to colleagues. 79% continue to use the booth to conduct swab tests. 92% liked that it offered swabber protection. 71% liked that the booth created a separate space for swabbing and 64% liked its ease of disinfection. 47% started swabbing only after receiving the booth and 58% said the booth was “important” or “very important” to their decision to participate in swab testing. However, 34% disliked that it took up too much space and the most frequently critiqued area was the gloves. Conclusion The human-centred design approach generated a product that had high user satisfaction, addressed GPs’ concerns of swabber protection and increased GPs’ participation in swab testing. The booth may be useful where GPs are concerned about swabber protection and space is limited.
INTRODUCTION:The effectiveness of cancer screening programmes is highly dependent on screening uptake. Many interventions have been tested to increase screening uptake. AIM:The goal of this study was to evaluate the effectiveness of cancer screening pamphlets as a standalone intervention. The outcome of interest was uptake of cancer screening tests. METHODS:A systematic review was performed on the effectiveness of pamphlets compared to usual care without pamphlets. We searched five databases for research papers in English from 2000 up to May 2019. Randomised controlled trials were included. This research group independently selected studies, extracted data, assessed risk of bias and then compared the information as a group. RESULTS:A total of nine trials involving 4912 participants met our inclusion criteria, of which five were about colorectal cancer screening, three were about prostate cancer screening and one was about lung cancer screening. Five of the nine trials showed that pamphlets alone increased uptake significantly, while the remaining four trials did not show significant effects. DISCUSSION:There is some evidence that pamphlets increase uptake for cancer screenings, especially for colorectal cancer. Due to the small number of studies in this area, generalisability could be limited.
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