DNA origami protection and molecular interfacing through engineered sequence-defined peptoids

DNA nanotechnology has established approaches for designing programmable and precisely controlled nanoscale architectures through specific Watson−Crick base-pairing, molecular plasticity, and intermolecular connectivity. In particular, superior control over DNA origami structures could be beneficial for biomedical applications, including biosensing, in vivo imaging, and drug and gene delivery. However, protecting DNA origami structures in complex biological fluids while preserving their structural characteristics remains a major challenge for enabling these applications. Here, we developed a class of structurally well-defined peptoids to protect DNA origamis in ionic and bioactive conditions and systematically explored the effects of peptoid architecture and sequence dependency on DNA origami stability. The applicability of this approach for drug delivery, bioimaging, and cell targeting was also demonstrated. A series of peptoids (PE1–9) with two types of architectures, termed as “brush” and “block,” were built from positively charged monomers and neutral oligo-ethyleneoxy monomers, where certain designs were found to greatly enhance the stability of DNA origami. Through experimental and molecular dynamics studies, we demonstrated the role of sequence-dependent electrostatic interactions of peptoids with the DNA backbone. We showed that octahedral DNA origamis coated with peptoid (PE2) can be used as carriers for anticancer drug and protein, where the peptoid modulated the rate of drug release and prolonged protein stability against proteolytic hydrolysis. Finally, we synthesized two alkyne-modified peptoids (PE8 and PE9), conjugated with fluorophore and antibody, to make stable DNA origamis with imaging and cell-targeting capabilities. Our results demonstrate an approach toward functional and physiologically stable DNA origami for biomedical applications

Gender Differences in Emergency Department (ED) Patient Mechanical Fall Risk and Openness to Communication with Providers

Gender Differences in Emergency Department (ED) Patient Mechanical Fall Risk and Openness to Communication with Providers Bryan G Kane, MD, Michael C Nguyen MD, Robert D Barraco, MD MPH, Brian Stello MD, Arnold Goldberg MD, Clare M Lenhart, PhD MPH, Bernadette G Porter BA ,Anita Kurt PhD, RN, Marna Rayl Greenberg DO, MPH Objectives: The CDC reports that among older adults (≥65), falls are the leading cause of injury-related death and rates of fall-related fractures among older women are more than twice those for men. We set out to determine ED patient perceptions (analyzed by gender) about their personal fall risk compared to their actual risk and their comfort level in discussing their fall history or a home safety plan with their healthcare provider. Methods: After IRB approval, a convenience sample of ED patients (50 years or older) was surveyed at a suburban Level 1 Trauma center with an annual ED census of approximately 75,000. The survey included demographics, the Falls Efficacy Scale (FES), and questions about fall risk. The FES is a validated survey measuring concern of falling. Analysis included descriptive statistics and assessment of fall risk and fear of falling by gender using chi-square and t-tests as indicated. Significance was set at 0.05. Results: Of the 150 surveys collected, 149 indicated gender and were included in this analysis. Fifty-five percent of the sample was female (n=82); 45% (n=67) were male. Most (98%) were Caucasian and 22% reported living alone. There was not a difference in the mean age of female participants 69.79 years (SD=12.08) vs. males 68.06 (SD=10.36; p=0.355). See Table 1 for distribution of reported fall risk factors between genders. Collectively, these variables resulted in a mean risk of falling score of 3.37(SD=1.62) out of 9. On average, female participants had a significantly higher objective risk of falling than did male participants (3.65 vs. 3.02 p=0.018). Similarly, females also reported greater fear of falling than did males (FES score 12.33 vs. 9.62; p=0.005). Significantly more females (41.5%) than males (23.9%, p=0.037) reported having fallen in the past year. Of the 50 participants reporting past-year falls, only 19 (12 female and 7 male, p=0.793) sought treatment. The correlation between actual fall risk and fear of falling were greater among females (p The majority of patients (76.4%) were willing to speak to a provider about their fall risk. No significant difference was noted in willingness to discuss this topic with a provider based on gender (p=0.619), objective fall risk (p=0.145) or FES score (p=0.986). Similarly, many respondents indicated a willing to discuss a home safety evaluation with a provider (58.1%) and responses did not vary significantly by gender (p=.140), objective fall risk (p=0.168) or FES score (p=.584). Conclusion: In this study, female ED patients reported a greater fear of falling, had a significantly higher objective risk of falling, and had a higher correlation between their perceived risk and actual risk of falling than did males. The majority of both genders were amenable to discussing their fall risk and a home safety evaluation with their provider

Modified CAGE as a Screening Tool for Mechanical Fall Risk Assessment: A Pilot Survey

Modified CAGE as a Screening Tool for Mechanical Fall Risk Assessment: A Pilot Survey Marna Rayl Greenberg DO, MPH, Michael C Nguyen MD, Bernadette G Porter BA,Robert DBarraco, MD MPH, Brian Stello MD, Arnold Goldberg MD, Clare M Lenhart, PhD MPH,Anita Kurt PhD, RN, Bryan G Kane, MD Background: Falls in the elderly cause serious injury. The literature does not hold answers to patient perceptions about their personal fall risk, their comfort level in discussing their fall history, or a home safety plan with their healthcare provider. Existing risk-assessing tools may be prohibitive in the Emergency Department due to their length and complexity. Objective: We piloted a modified CAGE screen (Fig1) to identify adults at risk for falls. Methods: At a community health event, a convenience sample ofparticipants (50 years or older) was surveyed. The survey included demographics, the Falls Efficacy Scale (FES), the modified CAGEand questions about fall risk.The FES is a validated, but longer, survey metric for comparison. A modified CAGE score greater than or equal to 1 was considered positive. Analysis included descriptive statistics and modified CAGE groups were compared by gender, fall risk and history with chi-square. Results: One hundred sevensubjects (66.4%female, 32.7% male) with a mean age of 66 (SD7.9)participated; 98 (91.6%)were Caucasian. Twenty (18.7%) lived alone,43 (40.2%) had a cat or dog, and 91 (85%) had stairs at home. Six (5.6%) reported using assistive devices, 2 (1.9%) at-risk alcohol use; 9 (8.4%)taking blood thinners, 50 (46.7%) taking blood pressure medications, and 22 (20.6%) one or more medications that could make them drowsy. Thirty-threesubjects(30.8%) reported having fallen in the past year; only13 (39.4% of those fallen)sought treatment. Collectively, these variables resulted in a mean risk of falling score of 2.49 (SD=1.36) out of 9. Eleven (31.4%)femalesand27 (38.0%)malesrecorded ≥1 positive responses on the modified CAGE.A modified CAGE positive responsewas significantly greater among those with past-year falls (51.5%) than those without (29.7%), p=0.031.A positive modified CAGE screen was also associated with a higher mean FES score (10.82 v7.83, p More females than males reported past year falls (36.6% vs. 17.1%, p=0.04) yet no difference in fall risk was noted between genders (4.44 vs. 4.26, p=0.506). The proportion of modified CAGE positive participants did not vary between females and males (38% vs. 31%, p=0.505). Of those whoscreened positive on the modified CAGE, 36 (92.3%) reported comfort in speaking to their healthcare provider about their fall risk and 26 (66.7%) in having a home safety evaluation. Conclusions: In this pilot, a positive modified CAGE is associated with both higher FES scores and a willingness to discuss fall risk with a health care provider. The modifiedCAGE may be a usefulbrief screening tool to detect fall risk in adults. Further studies to determine the extent of its utility in an Emergency Department should be considered