Here we propose a bio‐MEMS device designed to evaluate contractile force and conduction velocity of cell sheets in response to mechanical and electrical stimulation of the cell source as it grows to ...form a cellular sheet. Moreover, the design allows for the incorporation of patient‐specific data and cell sources. An optimized device would allow cell sheets to be cultured, characterized, and conditioned to be compatible with a specific patient's cardiac environment in vitro, before implantation. This design draws upon existing methods in the literature but makes an important advance by combining the mechanical and electrical stimulation into a single system for optimized cell sheet growth. The device has been designed to achieve cellular alignment, electrical stimulation, mechanical stimulation, conduction velocity readout, contraction force readout, and eventually cell sheet release. The platform is a set of comb electrical contacts consisting of three‐dimensional walls made of polydimethylsiloxane and coated with electrically conductive metals on the tops of the walls. Not only do the walls serve as a method for stimulating cells that are attached to the top, but their geometry is tailored such that they are flexible enough to be bent by the cells and used to measure force. The platform can be stretched via a linear actuator setup, allowing for simultaneous electrical and mechanical stimulation that can be derived from patient‐specific clinical data.
The proposed bio‐MEMS device has been designed to evaluate the contractile force and conduction velocity of cells in response to mechanical and electrical stimulation of the cell source as it grows to form a cellular sheet. The device geometry and stimulation profiles can be tailored to be patient specific and compatible with different cell types.
Invasion of the extracellular matrix is a critical step in the colonization of metastatic tumors. The invasion process is thought to be driven by both chemokine signaling and interactions between ...invading cancer cells and physical components of the metastatic niche, including endothelial cells that line capillary walls and serve as a barrier to both diffusion and invasion of the underlying tissue. Transwell chambers, a tool for generating artificial chemokine gradients to induce cell migration, have facilitated recent work to investigate the chemokine contributions to matrix invasion. These chambers, however, are poorly designed for imaging, which limits their use in investigating the physical cell-cell and cell-matrix interactions driving matrix invasion. Microfluidic devices offer a promising model in which the invasion process can be imaged. Many current designs, however, have limited surface areas and possess intricate geometries that preclude the use of standard staining protocols to visualize cells and matrix proteins. In this work, we present a novel microfluidic platform for imaging cell-cell and cell-matrix interactions driving metastatic cancer cell matrix invasion. Our model is applied to investigate how endothelial cell-secreted matrix proteins and the physical endothelial monolayer itself interact with invading metastatic breast cancer cells to facilitate invasion of an underlying type I collagen gel. The results show that matrix invasion of metastatic breast cancer cells is significantly enhanced in the presence of live endothelial cells. Probing this interaction further, our platform revealed that, while the fibronectin-rich matrix deposited by endothelial cells was not sufficient to drive invasion alone, metastatic breast cancer cells were able to exploit components of energetically inactivated endothelial cells to gain entry into the underlying matrix. These findings reveal novel cell-cell interactions driving a key step in the colonization of metastatic tumors and have important implications for designing drugs targeted at preventing cancer metastasis.
Mild cognitive impairment (MCI) is a prevalent symptom associated with the increased risk of dementia. There are many cognitive tests available for detection of MCI, and investigation of the ...diagnostic performance of the tests is deemed necessary.
This study aims to evaluate the diagnostic performance of different cognitive tests used for MCI detection.
A list of cognitive tests was identified in previous reviews and from online search engines. Literature searches were performed on each of the cognitive tests in MEDLINE, Embase, and PsycINFO from the earliest available dates of individual databases to December 31, 2016. Google Scholar was used as a supplementary search tool.
Studies that were used to assess the diagnostic performance of the cognitive tests were extracted with inclusion and exclusion criteria. Each test's performance was compared with the standard diagnostic criteria. Bivariate random effects models were used to summarize the test performance as a point estimate for sensitivity and specificity, and presented in a summary receiver operating characteristic curve. Reporting quality and risk of bias were evaluated.
A total of 108 studies with 23,546 participants were selected to evaluate 9 cognitive tests for MCI detection. Most of the studies used the Mini-Mental State Examination (MMSE) (n = 58) and the Montreal Cognitive Assessment (MoCA) (n = 35). The combined diagnostic performance of the MMSE in MCI detection was 0.71 sensitivity 95% confidence interval (CI): 0.66-0.75 and 0.74 specificity (95% CI: 0.70-0.78), and of the MoCA in MCI detection was 0.83 sensitivity (95% CI: 0.80-0.86) and 0.75 specificity (95% CI: 0.69-0.80). Among the 9 cognitive tests, recall tests showed the best diagnostic performance with 0.89 sensitivity (95% CI: 0.86-0.92) and 0.84 specificity (95% CI, 0.79-0.89). In subgroup analyses, long- or short-delay recall tests have shown better performance than immediate recall tests.
Recall tests were shown to be the most effective test in MCI detection, especially for the population with symptoms of memory deterioration. They can be potentially used as the triage screening test for MCI in primary care setting. But when a patient shows cognitive impairments beyond memory deterioration, a more comprehensive test such as the MoCA should be used.
Abstract Tailored biomaterials with tunable functional properties are desirable for many applications ranging from drug delivery to regenerative medicine. To improve the predictability of biopolymer ...materials functionality, multiple design parameters need to be considered, along with appropriate models. In this article we review the state of the art of synthesis and processing related to the design of biopolymers, with an emphasis on the integration of bottom-up computational modeling in the design process. We consider three prominent examples of well-studied biopolymer materials – elastin, silk, and collagen – and assess their hierarchical structure, intriguing functional properties and categorize existing approaches to study these materials. We find that an integrated design approach in which both experiments and computational modeling are used has rarely been applied for these materials due to difficulties in relating insights gained on different length- and time-scales. In this context, multiscale engineering offers a powerful means to accelerate the biomaterials design process for the development of tailored materials that suit the needs posed by the various applications. The combined use of experimental and computational tools has a very broad applicability not only in the field of biopolymers, but can be exploited to tailor the properties of other polymers and composite materials in general.
Increasing gender diversity in the STEM research workforce Greider, Carol W; Sheltzer, Jason M; Cantalupo, Nancy C ...
Science (American Association for the Advancement of Science),
11/2019, Letnik:
366, Številka:
6466
Journal Article
Recenzirano
Policies must address harassment and bias
Women experience substantial, gender-specific barriers that can impede their advancement in research careers. These include unconscious biases that ...negatively influence the perception of women's abilities, as well as social and cultural factors like those that lead to an unequal distribution of domestic labor (
1
,
2
). Additionally, sexual and gender-based harassment is a widespread and pernicious impediment to the retention and advancement of women in many science, technology, engineering, and mathematics (STEM)–related fields (
3
). Although there is substantial evidence documenting systemic barriers that women face in scientific careers, less is known about how research institutions and funding agencies can best address these problems (see references below and in the supplementary materials). We outline here specific, potentially high-impact policy changes that build upon existing mechanisms for research funding and governance and that can be rapidly implemented to counteract barriers facing women in science. These approaches must be coupled to vigorous and continuous outcomes-based monitoring, so that the most successful strategies can be disseminated and widely implemented. Though our professional focus is primarily academic biomedical research in U.S. institutions, we suggest that some of the approaches that we discuss may be broadly useful across STEM disciplines and outside of academia as well.
Virtual reality (VR) technology is a potential method to use in cognitive intervention, but the use of VR in cognitive stimulation intervention for older adults has not been investigated. Therefore, ...the aim of this study was to investigate the mood change of older adults after participating in the VR cognitive stimulation activity.
This is a multicenter randomized controlled, cross-over trial. The intervention was a VR cognitive stimulation activity, and the control was a paper-and-pencil activity. The participants were older adults with age over 60 and recruited in the elderly community centers. The Positive and Negative Affect Score (PANAS) was used to measure mood change. Mean difference (MD) with 95% confidence interval (95% CI) was calculated. The Simulator sickness questionnaire was used to measure adverse events.
A total of 236 participants from 19 community centers were recruited. After the VR activity, the participants had a significant increase in total PANAS positive affect score (MD = 2.09, 95% CI = 0.69 to 3.49), and a significant reduction in total negative affect score (MD = -1.99, 95% CI = -2.55 to -1.43). The reduction in negative affect score was significantly larger in VR activity than paper-and-pencil activity (MD = -0.48, 95% CI = -0.98 to 0.00). Besides, only three participants reported severe advance events after VR activity.
The use of VR technology is well accepted by older adults. Therefore, the use of VR technology through smartphone and a mobile app can be a potential method for future cognitive training interventions.
Background
Earlier studies suggest that probiotics have protective effects in the prevention of respiratory tract infections (RTIs). Whether such benefits apply to RTIs of viral origin and mechanisms ...supporting the effect remain unclear.
Aim
To determine the role of gut microbiota modulation on clinical and laboratory outcomes of viral RTIs.
Methods
We conducted a systematic review of articles published in Embase and MEDLINE through 20 April 2020 to identify studies reporting the effect of gut microbiota modulation on viral RTIs in clinical studies and animal models. The incidence of viral RTIs, clinical manifestations, viral load and immunological outcomes was evaluated.
Results
We included 58 studies (9 randomized controlled trials; 49 animal studies). Six of eight clinical trials consisting of 726 patients showed that probiotics administration was associated with a reduced risk of viral RTIs. Most commonly used probiotics were
Lactobacillus
followed by
Bifidobacterium
and
Lactococcus.
In animal models, treatment with probiotics before viral challenge had beneficial effects against influenza virus infection by improving infection-induced survival (20/22 studies), mitigating symptoms (21/21 studies) and decreasing viral load (23/25 studies). Probiotics and commensal gut microbiota exerted their beneficial effects through strengthening host immunity.
Conclusion
Modulation of gut microbiota represents a promising approach against viral RTIs via host innate and adaptive immunity regulation. Further research should focus on next generation probiotics specific to viral types in prevention and treatment of emerging viral RTIs.
In the United States, 1 in 10 infants are born preterm. The majority of neonatal deaths and nearly a third of infant deaths are linked to preterm birth. Preterm birth is initiated when the quiescent ...state of the uterus ends prematurely, leading to contractions and parturition beginning as early as 32 weeks, though the origins are not well understood. To enable research and discovery of therapeutics with potential to better address preterm birth, the capability to study isolated cell processes of pregnant uterine tissue in vitro is needed. Our development of an in vitro model of the myometrium utilizing human uterine smooth muscle cells (uSMCs) responsible for contractions provides a methodology to examine cellular mechanisms of late-stage pregnancy potentially involved in preterm birth. We discuss culture of uSMCs on a flexible polydimethylsiloxane (PDMS) substrate functionalized with cationic poly-l-lysine (PLL), followed by extracellular matrix (ECM) protein coating. Previous work exploring uSMC behavior on PDMS substrates have utilized collagen-I coatings, however, we demonstrated the first exploration of human uSMC response to strain on fibronectin-coated flexible membranes, importantly reflecting the significant increase of fibronectin content found in the myometrial ECM during late-stage pregnancy. Using the model we developed, we conducted proof-of-concept studies to investigate the impact of substrate strain on uSMC cell morphology and gene expression. It was found that PLL and varied ECM protein coatings (collagen I, collagen III, and fibronectin) altered cell nuclei morphology and density on PDMS substrates. Additionally, varied strain rates applied to uSMC substrates significantly impacted uSMC gene expression of IL-6, a cytokine associated with instances of preterm labor. These results suggest that both surface and mechanical properties of in vitro systems impact primary human uSMC phenotype and offer uSMC culture methodologies that can be utilized to further the understanding of cellular pathways involved in the uterus under mechanical load.
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•Uterine smooth muscle cells on fibronectin-treated surfaces for strain studies.•Poly-l-lysine on hydrophobic surfaces enhances uterine smooth muscle cell growth.•Strained uterine smooth muscle cells mimics pregnant myometrial microenvironment.•In vitro strain rate impacts IL-6, a marker for pre-term birth.•Electrolyte treatment of surface impacts uterine smooth muscle cell strain response.
The mechanical properties of spider silks drive interest as sources of new materials. However, there remains a lot to learn regarding the relationships between sequence, structure, and mechanical ...properties. In order to predict the types of sequence–functional relationships, synthesis–characterization–computation are integrated using recombinant spider silk‐like block copolymers. Two designs are studied, both with origins from the spider Nephila clavipes. These proteins are studied both experimentally and in silico to understand the relationships between sequence chemistry, processing, structure, and materials function. Films formed from the two proteins are thoroughly characterized. In parallel, molecular modeling is used to assess the propensity of the two sequences to form β‐sheets or crystalline structures. The results demonstrate that the modeling predicts the structural differences between the two silk‐like polymers and these features can also be related to differences in functional outcomes. With this example of relating sequence design (hydrophobic–hydrophilic domains), experiment (genetic design and synthesis), processing (film and fiber formation) and modeling (predictions of crystallinity), synergy among these methods is demonstrated for predictable material outcomes. This approach offers a robust discovery path when looking towards next generation approaches to targeted materials outcomes.
Understanding sequence–structure–property relationships provides the opportunity to generate materials with pre‐determined properties. A trinity approach combining controlled synthesis (genetically programmed), tailorable processing (via microfluidic focusing and film assembly), and molecular modeling with spider silk‐like designs as target materials is reported. This iterative approach offers a robust discovery path in optimizing material designs with predictable functional outcomes.
Abstract Children suffering from congenital heart defects (CHD) often require vascular reconstruction. Pediatric patients would greatly benefit from a cell-based tissue engineered vascular patch ...(TEVP) that has potential for growth. As artery structure and function are intimately linked, mimicking native tissue organization is an important design consideration. In this study, we cultured human mesenchymal stem cell on patterned thermo-responsive substrates. Cell alignment improved over time up to 2 wk in culture when sheets were ready for harvest. We then used cell sheets as “functional units” to build complex tissue structures that mimic native vascular smooth muscle cell organization in the medial layer of the artery. Cell sheets could be stacked using a gelatin stamp such that individual sheets in the construct were well aligned with each other (mimic of circumferential orientation) or at angles with respect to each other (mimic of herringbone structure). Controlling tissue organization layer-by-layer will be a powerful approach to building tissues with well defined and complex structure.
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