Enhanced Cell Killing by Paclitaxel-Loaded Recombinant Protein Micelles Bearing Integrin-Binding and Cell-Penetrating Peptides.

Peptide ligands are effective and specific vectors that can target cell surface receptors, and have shown great potential for targeting drug delivery vehicles. Often, materials used as drug delivery matrices are chemically synthesized and difficult to functionalize, which compromises their development as smart drug carriers. Here, we assemble carriers from a recombinant protein as a novel approach to overcome these limitations. We have previously shown that oleosin, a natural surfactant protein, can be engineered to self-assemble into spherical micelles, and that functionalizing oleosin with RGDS can increase cellular uptake in integrin bearing cells. Here, we investigated whether we could further enhance cellular by incorporating either a RGDS synergy peptide PHSRN or a cell-penetrating Tat peptide derived from human immunodeficiency virus (HIV). The resulting modified oleosins self-assemble into spherical micelles in aqueous environments. Spherical micelles made from oleosin can effectively encapsulate the hydrophobic chemotherapeutic drug paclitaxel (PX). After 15 hours, 350 nM PX loaded oleosin micelles equipped with both RGDS and Tat increased cell killing by twofold compared to free paclitaxel, and 1.2-fold compared to micelles made from RGD-oleosin alone. Micelles equipped with PHSRN alone does not facilitate cell killing compared to free paclitaxel, whereas micelles equipped with both PHSRN and RGDS increased cell killing by 1.1 fold compared to micelles with RGDS alone in 15 hours. Therefore, incorporating multiple motifs into oleosin is an approach for candidate for making a versatile drug delivery carrier.

Multidisciplinary meeting review in nonsmall cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Lung cancer diagnosis, staging and treatment may be enhanced by multidisciplinary participation and presentation in multidisciplinary meetings (MDM). We performed a systematic review and meta-analysis to explore literature evidence of clinical impacts of MDM exposure. METHODS: A study protocol was registered (PROSPERO identifier CRD42021258069). Randomised controlled trials and observational cohort studies including adults with nonsmall cell lung cancer and who underwent MDM review, compared to no MDM, were included. MEDLINE, CENTRAL, Embase and ClinicalTrials.gov were searched on 31 May 2021. Studies were screened and extracted by two reviewers. Outcomes included time to diagnosis and treatment, histological confirmation, receipt of treatments, clinical trial participation, survival and quality of life. Risk of bias was assessed using the ROBINS-I (Risk of Bias in Non-randomised Studies - of Interventions) tool. RESULTS: 2947 citations were identified, and 20 studies were included. MDM presentation significantly increased histological confirmation of diagnosis (OR 3.01, 95% CI 2.30-3.95; p<0.00001) and availability of clinical staging (OR 2.55, 95% CI 1.43-4.56; p=0.002). MDM presentation significantly increased likelihood of receipt of surgery (OR 2.01, 95% CI 1.29-3.12; p=0.002) and reduced the likelihood of receiving no active treatment (OR 0.32, 95% CI 0.21-0.50; p=0.01). MDM presentation was protective of both 1-year survival (OR 3.23, 95% CI 2.85-3.68; p<0.00001) and overall survival (hazard ratio 0.63, 95% CI 0.55-0.72; p<0.00001). DISCUSSION: MDM presentation was associated with increased likelihood of histological confirmation of diagnosis, documentation of clinical staging and receipt of surgery. Overall and 1-year survival was better in those presented to an MDM, although there was some clinical heterogeneity in participants and interventions delivered. Further research is required to determine the optimal method of MDM presentation, and address barriers to presentation.

Feasibility and Acceptability of Remote Neuromotor Rehabilitation Interactions Using Social Robot Augmented Telepresence: A Case Study.

There is a growing need to deliver rehabilitation care to patients remotely. Long term demographic changes, geographic shortages of care providers, and now a global pandemic contribute to this need. Telepresence provides an option for delivering this care. However, telepresence using video and audio alone does not provide an interaction of the same quality as in-person. To bridge this gap, we propose the use of social robot augmented telepresence (SRAT). We have constructed a demonstration SRAT system for upper extremity rehab, in which a humanoid, with a head, body, face, and arms, is attached to a mobile telepresence system, to collaborate with the patient and clinicians as an independent social entity. The humanoid can play games with the patient and demonstrate activities. These activities could be used to perform assessments in support of self-directed rehab and to perform exercises.In this paper, we present a case series with six subjects who completed interactions with the robot, three subjects who have previously suffered a stroke and three pediatric subjects who are typically developing. Subjects performed a Simon Says activity and a target touch activity in person, using classical telepresence (CT), and using SRAT. Subjects were able to effectively work with the social robot guiding interactions and 5 of 6 rated SRAT better than CT. This study demonstrates the feasibility of SRAT and some of its benefits.

The design of Lil'Flo, a socially assistive robot for upper extremity motor assessment and rehabilitation in the community via telepresence.

INTRODUCTION: We present Lil'Flo, a socially assistive robotic telerehabilitation system for deployment in the community. As shortages in rehabilitation professionals increase, especially in rural areas, there is a growing need to deliver care in the communities where patients live, work, learn, and play. Traditional telepresence, while useful, fails to deliver the rich interactions and data needed for motor rehabilitation and assessment. METHODS: We designed Lil'Flo, targeted towards pediatric patients with cerebral palsy and brachial plexus injuries using results from prior usability studies. The system combines traditional telepresence and computer vision with a humanoid, who can play games with patients and guide them in a present and engaging way under the supervision of a remote clinician. We surveyed 13 rehabilitation clinicians in a virtual usability test to evaluate the system. RESULTS: The system is more portable, extensible, and cheaper than our prior iteration, with an expressive humanoid. The virtual usability testing shows that clinicians believe Lil'Flo could be deployed in rural and elder care facilities and is more capable of remote stretching, strength building, and motor assessments than traditional video only telepresence. CONCLUSIONS: Lil'Flo represents a novel approach to delivering rehabilitation care in the community while maintaining the clinician-patient connection.

Perceived Usefulness of a Social Robot Augmented Telehealth Platform by Therapists in the United States.

With the shortage of rehabilitation clinicians in rural areas and the ongoing COVID-19 pandemic, remote rehabilitation (telerehab) fills an important gap in access to rehabilitation, especially for the treatment of adults and children experiencing upper arm disability due to stroke and cerebral palsy. We propose the use of a socially assistive robot with arms, a torso, and a face to play games with and guide patients, coupled with a telepresence platform, to maintain the patient-clinician interaction, and a computer vision system, to aid in automated objective assessments, as a tool for achieving more effective telerehab. In this paper, we outline the design of such a system, Lil'Flo, and present a uniquely large perceived usefulness evaluation of the Lil'Flo platform with 351 practicing therapists in the United States. We analyzed responses to the question of general interest and 5 questions on Lil'Flo's perceived usefulness. Therapists believe that Lil'Flo would significantly improve communication, motivation, and compliance during telerehab interactions when compared to traditional telepresence. 27% of therapists reported that they were interested in using Lil'Flo. Therapists interested in using Lil'Flo perceived it as having significantly higher usefulness across all measured dimensions than those who were not interested in using it.