A new tissue-agnostic microfluidic device to model physiology and disease: the lattice platform.

To accurately phenocopy human biology in vitro, researchers have been reducing their dependence on standard, static two-dimensional (2D) cultures and instead are moving towards three-dimensional (3D) and/or multicellular culture techniques. While these culture innovations are becoming more commonplace, there is a growing body of research that illustrates the benefits and even necessity of recapitulating the dynamic flow of nutrients, gas, waste exchange and tissue interactions that occur in vivo. However, cost and engineering complexity are two main factors that hinder the adoption of these technologies and incorporation into standard laboratory workflows. We developed LATTICE, a plug-and-play microfluidic platform able to house up to eight large tissue or organ models that can be cultured individually or in an interconnected fashion. The functionality of the platform to model both healthy and diseased tissue states was demonstrated using 3D cultures of reproductive tissues including murine ovarian tissues and human fallopian tube explants (hFTE). When exogenously exposed to pathological doses of gonadotropins and androgens to mimic the endocrinology of polycystic ovarian syndrome (PCOS), subsequent ovarian follicle development, hormone production and ovulation copied key features of this endocrinopathy. Further, hFTE cilia beating decreased significantly only when experiencing continuous media exchanges. We were then able to endogenously recreate this phenotype on the platform by dynamically co-culturing the PCOS ovary and hFTE. LATTICE was designed to be customizable with flexibility in 3D culture formats and can serve as a powerful automated tool to enable the study of tissue and cellular dynamics in health and disease in all fields of research.

Communication and Teamwork During Telemedicine-Enabled Stroke Care in an Ambulance.

OBJECTIVE: The purpose of this study is to understand the communication among care teams during telemedicine-enabled stroke consults in an ambulance. BACKGROUND: Telemedicine can have a significant impact on acute stroke care by enabling timely intervention in an ambulance before a patient reaches the hospital. However, limited research has been conducted on understanding and supporting team communication during the care delivery process for telemedicine-enabled stroke care in an ambulance. METHOD: Video recordings of 13 simulated stroke telemedicine consults conducted in an ambulance were coded to document the tasks, communication events, and flow disruptions during the telemedicine-enabled stroke care delivery process. RESULTS: The majority (82%) of all team interactions in telemedicine-enabled stroke care involved verbal interactions among team members. The neurologist, patient, and paramedic were almost equally involved in team interactions during stroke care, though the neurologist initiated 48% of all verbal interactions. Disruptions were observed in 8% of interactions, and communication-related issues contributed to 44%, with interruptions and environmental hazards being other reasons for disruptions in interactions during telemedicine-enabled stroke care. CONCLUSION: Successful telemedicine-enabled stroke care involves supporting both verbal and nonverbal communication among all team members using video and audio systems to provide effective coverage of the patient for the clinicians as well as vice versa. APPLICATION: This study provides a deeper understanding of team interactions during telemedicine-enabled stroke care that is essential for designing effective systems to support teamwork.

Comparing Sources of Disruptions to Telemedicine-Enabled Stroke Care in an Ambulance.

OBJECTIVE: The purpose of this study is to understand the nature and source of disruptions in an ambulance during the telemedicine-based caregiving process for stroke patients to enhance the ambulance design for supporting telemedicine-based care. BACKGROUND: Telemedicine is emerging as an efficient approach to provide timely remote assessment of patients experiencing acute stroke in an ambulance. These consults are facilitated by connecting the patient and paramedic with a remotely located neurologist and nurse using cameras, audio systems, and computers. However, ambulances are typically retrofitted to support telemedicine-enabled care, and the placement of these systems inside the ambulance might lead to spatial challenges and disruptions during patient evaluation. METHOD: Video recordings of 13 simulated telemedicine-based stroke consults were coded and analyzed using an existing systems-based flow disruption (FD) taxonomy. For each observed disruption-the type, severity or impact, location in the ambulance, and equipment involved in the disruption were recorded. RESULTS: Seat size, arrangement of assessment equipment, location of telemedicine equipment (computer workstation), and design of telemedicine camera were among the factors that impacted telemedicine-related disruptions. The left ambulance seat zone and head of the patient bed were more involved in environmental hazard-related disruptions, while the right zone of the ambulance was more prone to interruptions and communication-related disruptions. CONCLUSION: Adequate evaluation space for the paramedic, proper placement of evaluation equipment, and telemedicine computer location could facilitate the stroke care evaluation process and reduce FDs in the ambulance.

An exploratory study investigating the barriers, facilitators, and demands affecting caregivers in a telemedicine integrated ambulance-based setting for stroke care.

Telemedicine implementation in ambulances can reduce time to treatment for stroke patients, which is important as "time is brain" for these patients. Limited research has explored the demands placed on acute stroke caregivers in a telemedicine-integrated ambulance system. This study investigates the impact of telemedicine on workload, teamwork, workflow, and communication of geographically distributed caregivers delivering stroke care in ambulance-based telemedicine and usability of the system. Simulated stroke sessions were conducted with 27 caregivers, who subsequently completed a survey measuring workload, usability, and teamwork. Follow-up interviews with each caregiver ascertained how telemedicine affected workflow and demands which were analyzed for barriers and facilitators to using telemedicine. Caregivers experienced moderate workload and rated team effectiveness and usability high. Barriers included frustration with equipment and with the training of caregivers increasing demands, the loss of personal connection of the neurologists with the patients, and physical constraints in the ambulance. Facilitators were more common with live visual communication increasing teamwork and efficiency, the ease of access to neurologist, increased flexibility, and high overall satisfaction and usability. Future research should focus on eliminating these barriers and supporting the distributed cognition of caregivers.

Dental resins used in 3D printing technologies release ovo-toxic leachates.

We recently engineered the first female reproductive tract on a chip (EVATAR), to enable sex-based ex vivo research. To increase the scalability and accessibility of EVATAR, we turned to 3D printing (3DP) technologies, selecting two biocompatible 3DP resins, Dental SG (DSG) and Dental LT (DLT) to generate 3DP microphysiologic platforms. Due to the known sensitivity of reproductive cells to leachable compounds, we first screened for toxicity of these biomaterials using an in vitro mammalian oocyte maturation assay. Culture of mouse oocytes in 3DP plates using conventionally treated DSG resin resulted in rapid oocyte degeneration. Oxygen plasma treatment of the surface of printed DSG resin prevented this degeneration, and the majority of the resulting oocytes progressed through meiosis in vitro. However, 57.0% ± 37.2% of the cells cultured in the DSG resin plates exhibited abnormal chromosome morphology compared to 19.4% ± 17.3% of controls cultured in polystyrene. All tested DLT resin conditions, including plasma treatment, resulted in complete and rapid oocyte degeneration. To identify the ovo-toxic component of DLT, we analyzed DLT leachate using mass spectroscopy. We identified Tinuvin 292, a commercial light stabilizer, as a major component of the DLT leachate, which resulted in a dose-dependent disruption of meiotic progression and increase in chromosomal abnormalities with oocyte exposure, showing significant ovo-toxicity in mammals. Severe reproductive toxicity induced by in vitro exposure to these 3D-printed resins highlights potential risks of deploying insufficiently characterized materials for biomedical applications and underscores the need for more rigorous evaluation and designation of biocompatible materials.

Author Correction: Engineered reproductive tissues.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Engineered reproductive tissues.

Engineered male and female biomimetic reproductive tissues are being developed as autonomous in vitro units or as integrated multi-organ in vitro systems to support germ cell and embryo function, and to display characteristic endocrine phenotypic patterns, such as the 28-day human ovulatory cycle. In this Review, we summarize how engineered reproductive tissues facilitate research in reproductive biology, and overview strategies for making engineered reproductive tissues that might eventually allow the restoration of reproductive capacity in patients.

An Investigation of the Information Sought by Caregivers of Alzheimer's Patients on Online Peer Support Groups.

Caregivers of Alzheimer's patients find respite in online communities for solutions and emotional support. This study aims to understand the characteristics of information caregivers of Alzheimer's patients are searching for and the kind of support they receive through Internet-based peer support communities. Using a Web crawler written in Python Web programming language, we retrieved publicly available 2,500 random posts and their respective solutions from April 2012 to October 2016 on the solutions category of the Caregiver's Forum on ALZConnected.org . A content analysis was conducted on these randomly selected posts and 4,219 responses to those posts based on a classification system were derived from initial analyses of 750 posts and related responses. The results showed most posts (26%) related to queries about Alzheimer's symptoms, and the highest percentage of responses (45.56%) pertained to caregiver well-being. The LIWC analyses generated an average tone rating of 27.27 for the posts, implying a negative tone and 65.17 for their responses, implying a slightly positive tone. The ALZConnected.org Web site has the potential of being an emotionally supportive tool for caregivers; however, a more user-friendly interface is required to accommodate the needs of most caregivers and their technological skills. Solutions offered on the peer support groups are often subjective opinions of other caregivers and should not be considered professional or comprehensive; further research on educating caregivers using online forums is necessary.

A Systematic Review of the Implementation Challenges of Telemedicine Systems in Ambulances.

BACKGROUND: Telemedicine systems are gaining attention nationwide as a means for providing care in remote areas and allowing a small number of providers to impact a large geographic region. We systematically reviewed the literature to identify the efficacy and implementation challenges of telemedicine systems in ambulances. METHODS: A search for published studies on Web of Science and PubMed was completed. Studies were selected if they included at least a pilot study and they focused on feasibility or implementation of telemedicine systems in ambulances. RESULTS: A total of 864 articles were used for title and abstract screening. Full text screening was completed for 102 articles, with 23 being selected for final review. Sixty-one percent of the studies included in the review focused on general emergency care, while 26% focused on stroke care and 13% focused on myocardial infarction care. The reviewed studies found that telemedicine is feasible and effective in decreasing treatment times, report a high diagnosis accuracy rate, show higher rates of positive task completion than in regular ambulances, and demonstrate that stroke evaluation is completed with comparable accuracy to the standard way of delivering care. CONCLUSIONS: Although this review identified life-saving benefits of telemedicine, it also showed the paucity of the scientifically sound research in its implementation, prompting further studies. Further research is needed to analyze the capabilities and challenges involved in implementing telemedicine in ambulances, especially studies focusing on human-system integration and human factors' considerations in the implementation of telemedicine systems in ambulances, the development of advanced Internet connectivity paradigms, additional applications for triaging, and the implications of ambulance location.

Doxorubicin Has Dose-Dependent Toxicity on Mouse Ovarian Follicle Development, Hormone Secretion, and Oocyte Maturation.

Doxorubicin (DOX), one of the most commonly used anticancer medications, has been reported to affect fertility by damaging ovarian follicles; however, the dose-dependent toxicity of DOX on the dynamic follicle development and oocyte maturation has not been well-defined. Our objective is to determine the effects of human-relevant exposure levels of DOX on follicular functions across developmental time. In vitro cultured multilayered secondary mouse follicles were treated with DOX at 0, 2, 20, 100, and 200 nM for 24 h, and follicle development, hormone secretion, and oocyte maturation were analyzed. DOX caused dose-dependent toxicity on follicle growth, survival, and secretion of 17ß-estradiol (E2). At 200 nM, DOX induced DNA damage and apoptosis in follicle somatic cells first and then in oocytes, which was correlated with the uptake of DOX first to the somatic cells followed by germ cells. Follicles treated with DOX at 0, 2, and 20 nM showed similar oocyte metaphase II (MII) percentages after in vitro oocyte maturation; however, 20 nM DOX significantly increased the number of MII oocytes with abnormal spindle morphology and chromosome misalignment. In an effort to harmonize the in vitro study to in vivo treatment, dose-dependent toxicity on oocyte meiotic maturation was found in 16-day-old CD-1 mice treated with DOX at 0, 0.4, 2, and 10 mg/kg, consistent with the in vitro oocyte maturation outcomes. Our study demonstrates that DOX has dose-dependent toxicity on ovarian follicle development, hormone secretion, and oocyte maturation, which are three key factors to support the female reproductive and endocrine functions.

A microfluidic culture model of the human reproductive tract and 28-day menstrual cycle.

The endocrine system dynamically controls tissue differentiation and homeostasis, but has not been studied using dynamic tissue culture paradigms. Here we show that a microfluidic system supports murine ovarian follicles to produce the human 28-day menstrual cycle hormone profile, which controls human female reproductive tract and peripheral tissue dynamics in single, dual and multiple unit microfluidic platforms (Solo-MFP, Duet-MFP and Quintet-MPF, respectively). These systems simulate the in vivo female reproductive tract and the endocrine loops between organ modules for the ovary, fallopian tube, uterus, cervix and liver, with a sustained circulating flow between all tissues. The reproductive tract tissues and peripheral organs integrated into a microfluidic platform, termed EVATAR, represents a powerful new in vitro tool that allows organ-organ integration of hormonal signalling as a phenocopy of menstrual cycle and pregnancy-like endocrine loops and has great potential to be used in drug discovery and toxicology studies.

Designing Telemedicine Systems for Geriatric Patients: A Review of the Usability Studies.

BACKGROUND: One area where telemedicine may prove to be highly effective is in providing medical care to the geriatric population, an age group predicted to account for 20% of the population in the near future. However, even though telemedicine has certain advantages, the usability of these systems with this population merits investigation. MATERIALS AND METHODS: This article reviews the literature published from 2000 to 2016 with the goal of analyzing the characteristics of usability-related studies conducted using geriatric participants and the subsequent usability challenges identified. Articles were found using Web of Knowledge and PubMed citation indexing portals using the keywords (1) Telemedicine* AND Geriatrics* (2) Telemedicine* AND Usability* (3) Telemedicine* AND Usability* AND Older Adults*. RESULTS: A total of 297 articles were obtained from the initial search. After further detailed screening, 16 articles were selected for review based on the inclusion criteria. Of these, 60% of the studies focused on the overall usability of telemedicine systems; 6.25% focused on the usability of a telepresence robot; 12.5% compared a face-to-face medical consultation with the use of telemedicine systems, and 25% focused on the study of other aspects of telemedicine in addition to its usability. Findings reported in the studies included high patient satisfaction with telemedicine in 31.25%, whereas another 31.25% indicated a high acceptance of this method of medical consultation. Care coordination in 6.25% of the studies; confidence in telemedicine in 6.25%; trust, privacy, and reliability in 6.25%; and increased convenience when compared to personal visits in 18.75% were also reported. CONCLUSIONS: This review suggests limited research providing scientifically valid and reproducible usability evaluation at various stages of telemedicine system development. Telemedicine system designers need to consider the age-related issues in cognition, perception, and behavior of geriatric patients while designing telemedicine applications. Future directions for research were developed based on the limitations as well as other results found in this systematic review.

Exploiting Size-Dependent Drag and Magnetic Forces for Size-Specific Separation of Magnetic Nanoparticles.

Realizing the full potential of magnetic nanoparticles (MNPs) in nanomedicine requires the optimization of their physical and chemical properties. Elucidation of the effects of these properties on clinical diagnostic or therapeutic properties, however, requires the synthesis or purification of homogenous samples, which has proved to be difficult. While initial simulations indicated that size-selective separation could be achieved by flowing magnetic nanoparticles through a magnetic field, subsequent in vitro experiments were unable to reproduce the predicted results. Magnetic field-flow fractionation, however, was found to be an effective method for the separation of polydisperse suspensions of iron oxide nanoparticles with diameters greater than 20 nm. While similar methods have been used to separate magnetic nanoparticles before, no previous work has been done with magnetic nanoparticles between 20 and 200 nm. Both transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis were used to confirm the size of the MNPs. Further development of this work could lead to MNPs with the narrow size distributions necessary for their in vitro and in vivo optimization.