Macrophage polarization impacts tunneling nanotube formation and intercellular organelle trafficking.

Tunneling nanotubes (TNTs) are cellular extensions enabling cytosol-to-cytosol intercellular interaction between numerous cell types including macrophages. Previous studies of hematopoietic stem and progenitor cell (HSPC) transplantation for the lysosomal storage disorder cystinosis have shown that HSPC-derived macrophages form TNTs to deliver cystinosin-bearing lysosomes to cystinotic cells, leading to tissue preservation. Here, we explored if macrophage polarization to either proinflammatory M1-like M(LPS/IFNγ) or anti-inflammatory M2-like M(IL-4/IL-10) affected TNT-like protrusion formation, intercellular transport and, ultimately, the efficacy of cystinosis prevention. We designed new automated image processing algorithms used to demonstrate that LPS/IFNγ polarization decreased bone marrow-derived macrophages (BMDMs) formation of protrusions, some of which displayed characteristics of TNTs, including cytoskeletal structure, 3D morphology and size. In contrast, co-culture of macrophages with cystinotic fibroblasts yielded more frequent and larger protrusions, as well as increased lysosomal and mitochondrial intercellular trafficking to the diseased fibroblasts. Unexpectedly, we observed normal protrusion formation and therapeutic efficacy following disruption of anti-inflammatory IL-4/IL-10 polarization in vivo by transplantation of HSPCs isolated from the Rac2-/- mouse model. Altogether, we developed unbiased image quantification systems that probe mechanistic aspects of TNT formation and function in vitro, while HSPC transplantation into cystinotic mice provides a complex in vivo disease model. While the differences between polarization cell culture and mouse models exemplify the oversimplicity of in vitro cytokine treatment, they simultaneously demonstrate the utility of our co-culture model which recapitulates the in vivo phenomenon of diseased cystinotic cells stimulating thicker TNT formation and intercellular trafficking from macrophages. Ultimately, we can use both approaches to expand the utility of TNT-like protrusions as a delivery system for regenerative medicine

Adaptive Exercise Equipment

This document outlines the senior design project carried out by a team of mechanical engineering students at California Polytechnic State University, San Luis Obispo. The task is to design adapted exercise equipment for the non-profit organization, Achievement House. The objective of this Final Design Review is to document the final design, manufacturing plan, design verification plan, and project management plan. In addition, this document includes previously presented information on the project background, objectives, and concept design. The background and objective sections document various forms of customer research and include the project goals developed by the athletes and fitness instructors of Achievement House. This section has been updated to reflect new data involving athlete height, arm span, and wheelchair dimensions. The concept design section has been updated to reflect a singular combined apparatus, as recommended by our sponsor. The final design section outlines the final design of our project, including material selection, drawings, cost analysis, and safety considerations. The manufacturing plan section includes the steps we will take to verify our design through prototyping. The project management section outlines the next steps that must be taken in order to complete the project in the future

Prevalence of drug-herb and drug-supplement interactions in older adults : A cross-sectional survey

© British Journal of General PracticeBackground Polypharmacy is common among older adults, with increasing numbers also using prescription drugs with herbal medicinal products (HMPs) and dietary supplements. There is no reliable evidence from the UK on concurrent use of HMPs and dietary supplements with prescription drugs in older adults. Aim To establish prevalence of concurrent prescription drugs, HMPs, and dietary supplements among UK community-dwelling older adults and identify potential interactions. Design and setting Cross-sectional survey of older adults registered at two general practices in South East England. Method A questionnaire asking about prescription medications, HMPs, and sociodemographic information was posted to 400 older adults aged ≥65 years, identified as taking ≥1 prescription drug. Results In total 155 questionnaires were returned (response rate = 38.8%) and the prevalence of concurrent HMPs and dietary supplements with prescriptions was 33.6%. Females were more likely than males to be concurrent users (43.4% versus 22.5%; P = 0.009). The number of HMPs and dietary supplements ranged from 1 to 8, (mean = 3, median = 1; standard deviation = 1.65). The majority of concurrent users (78.0%) used dietary supplements with prescription drugs. The most commonly used dietary supplements were cod liver oil, glucosamine, multivitamins, and Vitamin D. Others (20.0%) used only HMPs with prescription drugs. Common HMPs were evening primrose oil, valerian, and Nytol Herbal® (a combination of hops, gentian, and passion flower). Sixteen participants (32.6%) were at risk of potential adverse drug interactions. Conclusion GPs should routinely ask questions regarding herbal and supplement use, to identify and manage older adults at potential risk of adverse drug interactions.Peer reviewe