Bounds in the Sensitivity of BioMEMS Devices for Cell Detection

This paper presents an ongoing effort to characterize performance and reliability of micro electromechanical systems used for biomedical diagnostics (BioMEMS). In order to study the interactions of human osteosarcoma (HOS) cells with BioMEMS devices, cultures were performed on silicon (Si) surfaces as well as silicon surfaces coated with 50 nm of titanium (Ti). Cell spreading on the surfaces was observed over time for up to 2 hours. It was seen that titanium coated silicon surfaces have the potential to provide a better interface for BioMEMS devices, due to enhanced adherence and spreading of the cells on these surfaces. Atomic force microscope (AFM) cantilevers were used as cell detection sensors. These cantilevers were coated with 50nm of titanium metal to provide a cell friendly surface. Theoretical models were then developed for the prediction of the vibrational responses of the AFM cantilevers before and after cell attachment. The models were used to relate the experimentally observed changes in frequency to the number of cells that are attached on the cantilever. The bounds in the possible frequency changes were determined within a theoretical framework. From experimentally calculated values for the mass of cells, random number simulations were carried out to determine the probability of cell attachment as a function of the change in resonance frequency of the cantilever sensor. The implications of the results are then discussed for the future reliability modeling of the sensor.     

Bio-inspired design of dental multilayers: Experiments and model

This paper combines experiments, simulations and analytical modeling that are inspired by the stress reductions associated with the functionally graded structures of the dentin–enamel-junctions (DEJs) in natural teeth. Unlike conventional crown structures in which ceramic crowns are bonded to the bottom layer with an adhesive layer, real teeth do not have a distinct “adhesive layer” between the enamel and the dentin layers. Instead, there is a graded transition from enamel to dentin within a 10 to 100 μm thick regime that is called the Dentin Enamel Junction (DEJ). In this paper, a micro-scale, bio-inspired functionally graded structure is used to bond the top ceramic layer (zirconia) to a dentin-like ceramic-filled polymer substrate. The bio-inspired functionally graded material (FGM) is shown to exhibit higher critical loads over a wide range of loading rates. The measured critical loads are predicted using a rate dependent slow crack growth (RDEASCG) model. The implications of the results are then discussed for the design of bio-inspired dental multilayers.     

An investigation of adhesion in drug-eluting stent layers

An atomic force microscopy (AFM) method was developed to quantify the adhesion forces between and cohesive forces within the layers of a drug-eluting stent (DES). Surface pairs representing both the individual components and the complete chemistry of each layer within the DES were prepared. As a model, the CYPHER Sirolimus-eluting Coronary Stent was studied. This DES consists of a stainless steel stent substrate, a parylene C primer layer, and a drug-eluting layer that contains poly(ethylene-co-vinyl acetate), poly(n-butyl methacrylate), and sirolimus (rapamycin). Coated AFM tips and two-dimensional substrates or coupons, which act as surrogates to the CYPHER Stent, were prepared and characterized. The force-displacement measurements were conducted to evaluate the adhesion between the middle parylene C layer and the 316L stainless steel substrate, the adhesion between the parylene C layer and the outer drug-eluting layer, and the cohesion between the three constituents of the drug-eluting layer. The average adhesion forces between the parylene C to drug layer varied from 88 to 167 nN, and the drug layer-to-drug layer interactions were between 194 and 486 nN within the model CYPHER Stent coating. All the adhesion forces measured were larger than those observed for gold-gold interactions, which yielded a pull of force of 19 nN (Zong et al., J Appl Phys 2006;100:104313-104323).     

Psychosocial interventions for improving engagement in care and health and behavioural outcomes for adolescents and young people living with HIV: a systematic review and meta‐analysis

IntroductionAdolescents and young people comprise a growing proportion of new HIV infections globally, yet current approaches do not effectively engage this group, and adolescent HIV‐related outcomes are the poorest among all age groups. Providing psychosocial interventions incorporating psychological, social, and/or behavioural approaches offer a potential pathway to improve engagement in care and health and behavioural outcomes among adolescents and young people living with HIV (AYPLHIV).MethodsA systematic search of all peer‐reviewed papers published between January 2000 and July 2020 was conducted through four electronic databases (Cochrane Library, PsycINFO, PubMed and Scopus). We included randomized controlled trials evaluating psychosocial interventions aimed at improving engagement in care and health and behavioural outcomes of AYPLHIV aged 10 to 24 years.Results and discussionThirty relevant studies were identified. Studies took place in the United States (n = 18, 60%), sub‐Saharan Africa (Nigeria, South Africa, Uganda, Zambia, Zimbabwe) and Southeast Asia (Thailand). Outcomes of interest included adherence to antiretroviral therapy (ART), ART knowledge, viral load data, sexual risk behaviours, sexual risk knowledge, retention in care and linkage to care. Overall, psychosocial interventions for AYPLHIV showed important, small‐to‐moderate effects on adherence to ART (SMD = 0.3907, 95% CI: 0.1059 to 0.6754, 21 studies, n = 2647) and viral load (SMD = −0.2607, 95% CI −04518 to −0.0696, 12 studies, n = 1566). The psychosocial interventions reviewed did not demonstrate significant impacts on retention in care (n = 8), sexual risk behaviours and knowledge (n = 13), viral suppression (n = 4), undetectable viral load (n = 5) or linkage to care (n = 1) among AYPLHIV. No studies measured transition to adult services. Effective interventions employed various approaches, including digital and lay health worker delivery, which hold promise for scaling interventions in the context of COVID‐19.ConclusionsThis review highlights the potential of psychosocial interventions in improving health outcomes in AYPLHIV. However, more research needs to be conducted on interventions that can effectively reduce sexual risk behaviours of AYPLHIV, as well as those that can strengthen engagement in care. Further investment is needed to ensure that these interventions are cost‐effective, sustainable and resilient in the face of resource constraints and global challenges such as the COVID‐19 pandemic.     

For the surgeon: an introduction to nanotechnology

BACKGROUND: The study and application of nanoparticles is advancing rapidly within medicine and surgery. In this article, we review nanotechnology with a view as to its impact on surgery. We also review potential toxicity, current regulations, and ethical considerations. DATA SOURCES: A Medline review of nanotechnology and nanosurgery was performed. Important publications in the history of the science and demonstrated important concepts were selected for review. CONCLUSION: Nanotechnology is a relatively new but fast evolving field. Its potential impact on medicine and surgery is expanding in areas from drug delivery to rudimentary nanosurgery at the cellular level. This review is written to give the surgeon an overview of the field particularly in reference to its potential surgical applications.     

Bond strengths, degree of conversion of the cement and molecular structure of the adhesive-dentine joint in fibre post restorations

Objectives

Because fibre post restorations are influenced by multiple factors such as the types of bonding materials, the dentine region and the time under moist exposure, this study sought to determine the bond strength of endodontic restorations and its relation to the degree of conversion of the cement layer and the molecular structure of the dentine-bonded joints.

Methods

The performance of 2 etch-and-rinse (All-Bond 2 and One-Step Plus) and 2 self-etch (Clearfil SE Bond and Xeno III) adhesives at post spaces regions, after 7 d or 4 m, was evaluated. FRC Postec Plus posts were cemented to the root canal with a dual-cure resin cement (Duo-Link). Transverse sections of the tooth were subjected to push-out testing, to degree-of-conversion measurements and to hybrid layer evaluation through μ-Raman spectroscopy.

Results

Coronal bonding was higher than cervical and middle bonding. The hybrid layer was thicker for the etch-and-rinse systems, with thicknesses decreasing towards the middle region. The degree of conversion measured for the 3-step etch-and-rinse group after 4 m was significantly higher than that for the self-etching groups.

Conclusions

Although not totally stable at the adhesive–dentine interface, the 3-step etch-and-rinse adhesive in the coronal dentine provided the best bond strength, degree of conversion of the cement and hybrid layer thickness in post restorations, in both short- and long-term analyses.     

Cell/surface interactions and adhesion on Ti-6Al-4V: effects of surface texture

This paper presents the results of an experimental study of the effects of surface texture on the interactions between human osteo-sarcoma (HOS) cells and Ti-6Al-4V. These include the Ti-6Al-4V with polished (smooth); Al(2)O(3) blasted (rough); and laser micro-grooved geometries with controlled spacings and depths. Immuno-fluorescence staining of adhesion proteins (actin and vinculin) was used to study the spreading and adhesion of HOS cells in 2 day culture experiments. Quantitative measures of adhesion were also obtained using an enzymatic detachment assay. The results are discussed within the context of existing theories of cell adhesion. The implications of the results are also examined for the design of textured surfaces in biomedical systems.     

LHRH-conjugated Magnetic Iron Oxide Nanoparticles for Detection of Breast Cancer Metastases

Summary Targeted delivery of superparamagnetic iron oxide nanoparticles (SPIONs) could facilitate their accumulation in metastatic cancer cells in peripheral tissues, lymph nodes and bones and enhance the sensitivity of magnetic resonance imaging (MRI). The specificities of luteinizing hormone releasing hormone (LHRH) and luteinizing hormone/chorionic gonadotropin (LH/CG)- bound SPIONs were tested in human breast cancer cells in vitro and were found to be dependent on the receptor expression of the target cells, the time of incubation and showed saturation kinetics. In incubations with MDA-MB-435S.luc cells, the highest iron accumulation was 452.6 pg Fe/cell with LHRH-SPIONs, 203.6 pg Fe/cell with β-CG-SPIONs and 51.3 pg Fe/cell with SPIONs. Incubations at 4 °C resulted in 1.1 pg Fe/cell. Co-incubation with the same ligands (βCG or LHRH) decreased the iron accumulation in each case. LHRH-SPIONs were poorly incorporated by macrophages. Tumors and metastatic cells from breast cancer xenografts were targeted in vivo in a nude mouse model. LHRH-SPION specifically accumulated in cells of human breast cancer xenografts. The amount of LHRH-SPION in the lungs was directly dependent on the number of metastatic cells and amounted to 77.8 pg Fe/metastastic cell. In contrast, unconjugated SPIONs accumulated in the liver, showed poor affinity to the tumor, and were not detectable in metastatic lesions in the lungs. LHRH-SPION accumulated in the cytosolic compartment of the target cells and formed clusters. LHRH-SPIONs did not accumulate in livers of normal mice. In conclusion, LHRH conjugated SPIONs may serve as a contrast agent for MR imaging in vivo and increase the sensitivity for the detection of metastases and disseminated cells in lymph nodes, bones and peripheral organs.