Increasingly, in vitro culture of adherent cell types utilizes three-dimensional (3D) scaffolds or aggregate culture strategies to mimic tissue-like, microenvironmental conditions. In parallel, new flow cytometry-based technologies are emerging to accurately analyze the composition and function of these microtissues (i.e., large particles) in a non-invasive and high-throughput way. Lacking, however, is an accessible platform that can be used to effectively sort or purify large particles based on analysis parameters. Here we describe a microfluidic-based, electromechanical approach to sort large particles. Specifically, sheath-less asymmetric curving channels were employed to separate and hydrodynamically focus particles to be analyzed and subsequently sorted. This design was developed and characterized based on wall shear stress, tortuosity of the flow path, vorticity of the fluid in the channel, sorting efficiency and enrichment ratio. The large particle sorting device was capable of purifying fluorescently labelled embryoid bodies (EBs) from unlabelled EBs with an efficiency of 87.3% 6 13.5%, and enrichment ratio of 12.2 6 8.4 (n ¼ 8), while preserving cell viability, differentiation potential, and long-term function. V C 2012 American Institute of Physics. [http://dx

BackgroundAdvanced prostate cancers that are resistant to all current therapies create a need for new therapeutic strategies. One recent innovative approach to cancer therapy is the simultaneous use of multiple FDA-approved drugs to target multiple pathways. A challenge for this approach is caused by the different solubility requirements of each individual drug, resulting in the need for a drug vehicle that is non-toxic and capable of carrying multiple water-insoluble antitumor drugs. Micelles have recently been shown to be new candidate drug solubilizers for anti cancer therapy.MethodsThis study set out to examine the potential use of multi-drug loaded micelles for prostate cancer treatment in preclinical models including cell line and mouse models for prostate cancers with Pten deletions. Specifically antimitotic agent docetaxel, mTOR inhibitor rapamycin, and HSP90 inhibitor 17-N-allylamino-17-demethoxygeldanamycin were incorporated into the micelle system (DR17) and tested for antitumor efficacy.ResultsIn vitro growth inhibition of prostate cancer cells was greater when all three drugs were used in combination compared to each individual drug, and packaging the drugs into micelles enhanced the cytotoxic effects. At the molecular level DR17 targeted simultaneously several molecular signaling axes important in prostate cancer including androgen receptor, mTOR, and PI3K/AKT. In a mouse genetic model of prostate cancer, DR17 treatment decreased prostate weight, which was achieved by both increasing caspase-dependent cell death and decreasing cell proliferation. Similar effects were also observed when DR17 was administered to nude mice bearing prostate cancer cells xenografts.ConclusionThese results suggest that combining these three cancer drugs in multi-drug loaded micelles may be a promising strategy for prostate cancer therapy.

Background Rates of opioid prescribing tripled in the United States between 1999 and 2015 and were associated with significant increases in opioid misuse and overdose death. Roughly half of all opioids are prescribed in primary care. Although clinical guidelines describe recommended opioid prescribing practices, implementing these guidelines in a way that balances safety and effectiveness vs. risk remains a challenge. The literature offers little help about which implementation strategies work best in different clinical settings or how strategies could be tailored to optimize their effectiveness in different contexts. Systems consultation consists of: (1) educational/engagement meetings with audit and feedback reports, (2) practice facilitation, and (3) prescriber peer consulting. The study is designed to discover the most cost-effective sequence and combination of strategies for improving opioid prescribing practices in diverse primary care clinics. Methods/DesignThe study is a hybrid type 3 clustered, sequential, multiple-assignment randomized trial (SMART) that randomizes clinics from two health systems at two points, months 3 and 9, of a 21month intervention. Clinics are provided one of four sequences of implementation strategies: a condition consisting of educational/engagement meetings and audit and feedback alone (EM/AF), EM/AF plus practice facilitation (PF), EM/AF + prescriber peer consulting (PPC), and EM/AF + PF + PPC.The study's primary outcome is morphine-milligram equivalent (MME) dose by prescribing clinicians within clinics. The study's primary aim is the comparison of EM/AF + PF + PPC versus EM/AF alone on change in MME from month 3 to month 21. The secondary aim is to derive cost estimates for each of the four sequences and compare them. The exploratory aim is to examine four tailoring variables that can be used to construct an adaptive implementation strategy to meet the needs of different primary care clinics.Discussion Systems consultation is a practical blend of implementation strategies used in this case to improve opioid prescribing practices in primary care. The blend offers a range of strategies in sequences from minimally to substantially intensive. The results of this study promise to help us understand how to cost effectively improve the implementation of evidence-based practices. Trial registration NCT 04044521 (ClinicalTrial.gov). Registered 05 August 2019. increasing the speed and efficiency of delivering evidence-based practices into health systems. Abbreviations AF, audit and feedback EBP, evidence-based practice EM, educational/engagement meeting EHR, electronic health record MME, morphine-milligram equivalent dose PF, practice facilitation PPC, prescriber peer consulting RE-AIM, Reach, Effectiveness, Adoption, Implementation, and Maintenance SMART, sequential, multiple-assignment randomized trial Declarations Ethics approval and consent to participate