Nanodiamond preparation and surface characterization for biological applications

Nanodiamonds contain stable fluorescent emitters and hence can be used for molecular fluorescence imaging and precision sensing of electromagnetic fields. The physical properties of these emitters together with their low reported cytotoxicity make them attractive for biological imaging applications. The controlled application of nanodiamonds for cellular imaging requires detailed understanding of surface chemistry, size ranges and aggregation, as these can all influence cellular interactions. We compared these characteristics for graphitic and oxidized nanodiamonds. Oxidation is generally used for surface functionalization, and was optimized by Thermogravimetric Analysis, achieved by 445±5°C heating in air for 5 hours, then confirmed via Raman and Infrared spectroscopies. Size ranges and aggregation were assessed using Atomic Force Microscopy and Dynamic Light Scattering. Biocompatibility in breast cancer cell lines was measured using a proliferation assay. Heating at 445±5°C reduced the Raman signal of graphitic carbon (1575 cm-1) as compared to that of diamond (1332 cm-1) from 0.31±0.07 Raman intensity units to 0.07±0.04. This temperature was substantially below the onset of major mass loss (observed at 535±1°C) and therefore achieved cost efficiency, convenience and high yield. Graphitic and oxidized nanodiamonds formed aggregates in water, with a mean particle size of 192±4nm and 166±2nm at a concentration of 66μg/mL. We then applied the graphitic and oxidized nanodiamonds to cells in culture at 1μg/mL and found no significant change in the proliferation rate (-5±2% and -1±3% respectively). Nanodiamonds may therefore be suitable for development as a novel transformative tool in the life sciences

Feasibility of silica-hybridized collagen hydrogels as three-dimensional cell matrices for hard tissue engineering

Exploiting hydrogels for the cultivation of stem cells, aiming to provide them with physico-chemical cues suitable for osteogenesis, is a critical demand for bone engineering. Here, we developed hybrid compositions of collagen and silica into hydrogels via a simple sol-gel process. The physico-chemical and mechanical properties, degradation behavior, and bone-bioactivity were characterized in-depth; furthermore, the in vitro mesenchymal stem cell growth and osteogenic differentiation behaviors within the 3D hybrid gel matrices were communicated for the first time. The hydrolyzed and condensed silica phase enabled chemical links with the collagen fibrils to form networked hybrid gels. The hybrid gels showed improved chemical stability and greater resistance to enzymatic degradation. The in vitro apatite-forming ability was enhanced by the hybrid composition. The viscoelastic mechanical properties of the hybrid gels were significantly improved in terms of the deformation resistance to an applied load and the modulus values under a dynamic oscillation. Mesenchymal stem cells adhered well to the hybrid networks and proliferated actively with substantial cytoskeletal extensions within the gel matrices. Of note, the hybrid gels substantially reduced the cell-mediated gel contraction behaviors, possibly due to the stiffer networks and higher resistance to cell-mediated degradation. Furthermore, the osteogenic differentiation of cells, including the expression of bone-associated genes and protein, was significantly upregulated within the hybrid gel matrices. Together with the physico-chemical and mechanical properties, the cellular behaviors observed within 3D gel matrices, being different from the previous approaches reported on 2D substrates, provide new information on the feasibility and usefulness of the silica-collagen system for stem cell culture and tissue engineering of hard tissues

Dual actions of osteoclastic-inhibition and osteogenic-stimulation through strontium-releasing bioactive nanoscale cement imply biomaterial-enabled osteoporosis therapy

Repair of defective hard-tissues in osteoporotic patients faces significantly challenges with limited therapeutic options. Although biomedical cements are considered promising materials for healthy bone repair, their uses for healing osteoporotic fracture are clinically limited. Herein, strontium-releasing-nanoscale cement was introduced to provide dual therapeutic-actions (pro-osteogenesis and anti-osteoclastogenesis), eventually for the regeneration of osteoporotic bone defect. The Sr-nanocement hardened from the Sr-doped nanoscale-glass particles was shown to release multiple ions including silicate, calcium and strontium at doses therapeutically relevant over time. When the Sr-nanocement was treated to pre-osteoblastic cells, the osteogenic mRNA level (Runx2, Opn, Bsp, Ocn), alkaline phosphatase activity, calcium deposition, and target luciferase reporter were stimulated with respect to the case with Sr-free-nanocement. When treated to pre-osteoclastic cells, the Sr-nanocement substantially reduced the osteoclastogenesis, such as osteoclastic mRNA level (Casr, Nfatc1, c-fos, Acp, Ctsk, Mmp-9), tartrate-resistant acid trap activity, and bone resorption capacity. In particular, the osteoclastic inhibition resulted in part from the interactive effect of osteoblasts which were activated by the Sr-nanocement, i.e., blockage of RANKL (receptor activator of nuclear factor-κB ligand) binding by enhanced osteoprotegerin and the deactivated Nfatc1. The Sr-nanocement, administered to an ovariectomized tibia defect (osteoporotic model) in rats, exhibited profound bone regenerative potential in cortical and surrounding trabecular area, including increased bone volume and density, enhanced production of osteopromotive proteins, and more populated osteoblasts, together with reduced signs of osteoclastic bone resorption. These results demonstrate that Sr-nanocement, with its dual effects of osteoclastic inhibition and osteogenic-stimulation, can be considered an effective nanotherapeutic implantable biomaterial platform for the treatment of osteoporotic bone defects

Carbon-nanotube-interfaced glass fiber scaffold for regeneration of transected sciatic nerve.

Carbon nanotubes (CNTs), with their unique and unprecedented properties, have become very popular for the repair of tissues, particularly for those requiring electrical stimuli. Whilst most reports have demonstrated in vitro neural cell responses of the CNTs, few studies have been performed on the in vivo efficacy of CNT-interfaced biomaterials in the repair and regeneration of neural tissues. Thus, we report here for the first time the in vivo functions of CNT-interfaced nerve conduits in the regeneration of transected rat sciatic nerve. Aminated CNTs were chemically tethered onto the surface of aligned phosphate glass microfibers (PGFs) and CNT-interfaced PGFs (CNT-PGFs) were successfully placed into three-dimensional poly(l/d-lactic acid) (PLDLA) tubes. An in vitro study confirmed that neurites of dorsal root ganglion outgrew actively along the aligned CNT-PGFs and that the CNT interfacing significantly increased the maximal neurite length. Sixteen weeks after implantation of a CNT-PGF nerve conduit into the 10mm gap of a transected rat sciatic nerve, the number of regenerating axons crossing the scaffold, the cross-sectional area of the re-innervated muscles and the electrophysiological findings were all significantly improved by the interfacing with CNTs. This first in vivo effect of using a CNT-interfaced scaffold in the regeneration process of a transected rat sciatic nerve strongly supports the potential use of CNT-interfaced PGFs at the interface between the nerve conduit and peripheral neural tissues

Evidence of the Importance of Host Habitat Use in Predicting the Dilution Effect of Wild Boar for Deer Exposure to Anaplasma spp

Foci of tick-borne pathogens occur at fine spatial scales, and depend upon a complex arrangement of factors involving climate, host abundance and landscape composition. It has been proposed that the presence of hosts that support tick feeding but not pathogen multiplication may dilute the transmission of the pathogen. However, models need to consider the spatial component to adequately explain how hosts, ticks and pathogens are distributed into the landscape

Histo-Blood Group Gene Polymorphisms as Potential Genetic Modifiers of Infection and Cystic Fibrosis Lung Disease Severity

The pulmonary phenotype in cystic fibrosis (CF) is variable; thus, environmental and genetic factors likely contribute to clinical heterogeneity. We hypothesized that genetically determined ABO histo-blood group antigen (ABH) differences in glycosylation may lead to differences in microbial binding by airway mucus, and thus predispose to early lung infection and more severe lung disease in a subset of patients with CF. infection in the severe or mild groups. Multivariate analyses of other clinical phenotypes, including gender, asthma, and meconium ileus demonstrated no differences between groups based on ABH type. infection, nor was there any association with other clinical phenotypes in a group of 808 patients homozygous for the ΔF508 mutation

Does the mind map learning strategy facilitate information retrieval and critical thinking in medical students?

<p>Abstract</p> <p>Background</p> <p>A learning strategy underutilized in medical education is mind mapping. Mind maps are multi-sensory tools that may help medical students organize, integrate, and retain information. Recent work suggests that using mind mapping as a note-taking strategy facilitates critical thinking. The purpose of this study was to investigate whether a relationship existed between mind mapping and critical thinking, as measured by the Health Sciences Reasoning Test (HSRT), and whether a relationship existed between mind mapping and recall of domain-based information.</p> <p>Methods</p> <p>In this quasi-experimental study, 131 first-year medical students were randomly assigned to a standard note-taking (SNT) group or mind map (MM) group during orientation. Subjects were given a demographic survey and pre-HSRT. They were then given an unfamiliar text passage, a pre-quiz based upon the passage, and a 30-minute break, during which time subjects in the MM group were given a presentation on mind mapping. After the break, subjects were given the same passage and wrote notes based on their group (SNT or MM) assignment. A post-quiz based upon the passage was administered, followed by a post-HSRT. Differences in mean pre- and post-quiz scores between groups were analyzed using independent samples <it>t</it>-tests, whereas differences in mean pre- and post-HSRT total scores and subscores between groups were analyzed using ANOVA. Mind map depth was assessed using the Mind Map Assessment Rubric (MMAR).</p> <p>Results</p> <p>There were no significant differences in mean scores on both the pre- and post-quizzes between note-taking groups. And, no significant differences were found between pre- and post-HSRT mean total scores and subscores.</p> <p>Conclusions</p> <p>Although mind mapping was not found to increase short-term recall of domain-based information or critical thinking compared to SNT, a brief introduction to mind mapping allowed novice MM subjects to perform similarly to SNT subjects. This demonstrates that medical students using mind maps can successfully retrieve information in the short term, and does not put them at a disadvantage compared to SNT students. Future studies should explore longitudinal effects of mind-map proficiency training on both short- and long-term information retrieval and critical thinking.</p

Imaging Immune and Metabolic Cells of Visceral Adipose Tissues with Multimodal Nonlinear Optical Microscopy

Visceral adipose tissue (VAT) inflammation is recognized as a mechanism by which obesity is associated with metabolic diseases. The communication between adipose tissue macrophages (ATMs) and adipocytes is important to understanding the interaction between immunity and energy metabolism and its roles in obesity-induced diseases. Yet visualizing adipocytes and macrophages in complex tissues is challenging to standard imaging methods. Here, we describe the use of a multimodal nonlinear optical (NLO) microscope to characterize the composition of VATs of lean and obese mice including adipocytes, macrophages, and collagen fibrils in a label-free manner. We show that lipid metabolism processes such as lipid droplet formation, lipid droplet microvesiculation, and free fatty acids trafficking can be dynamically monitored in macrophages and adipocytes. With its versatility, NLO microscopy should be a powerful imaging tool to complement molecular characterization of the immunity-metabolism interface

How to improve medical education website design

<p>Abstract</p> <p>Background</p> <p>The Internet provides a means of disseminating medical education curricula, allowing institutions to share educational resources. Much of what is published online is poorly planned, does not meet learners' needs, or is out of date.</p> <p>Discussion</p> <p>Applying principles of curriculum development, adult learning theory and educational website design may result in improved online educational resources. Key steps in developing and implementing an education website include: 1) Follow established principles of curriculum development; 2) Perform a needs assessment and repeat the needs assessment regularly after curriculum implementation; 3) Include in the needs assessment targeted learners, educators, institutions, and society; 4) Use principles of adult learning and behavioral theory when developing content and website function; 5) Design the website and curriculum to demonstrate educational effectiveness at an individual and programmatic level; 6) Include a mechanism for sustaining website operations and updating content over a long period of time.</p> <p>Summary</p> <p>Interactive, online education programs are effective for medical training, but require planning, implementation, and maintenance that follow established principles of curriculum development, adult learning, and behavioral theory.</p