Nanoparticle-based contrast agents are quickly becoming valuable and potentially transformative tools for enhancing medical diagnostics for a wide range of in-vivo imaging modalities. Compared with conventional molecular-scale contrast agents, nanoparticles (NPs) promise improved abilities for in-vivo detection and potentially enhanced targeting efficiencies through longer engineered circulation times, designed clearance pathways, and multimeric binding capacities. However, NP contrast agents are not without issues. Difficulties in minimizing batch-to-batch variations and problems with identifying and characterizing key physicochemical properties that define the in-vivo fate and transport of NPs are significant barriers to the introduction of new NP materials as clinical contrast agents. This manuscript reviews the development and application of nanoparticles and their future potential to advance current and emerging clinical bioimaging techniques. A focus is placed on the application of solid, phase-separated materials, for example metals and metal oxides, and their specific application as contrast agents for in-vivo near-infrared fluorescence (NIRF) imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), ultrasound (US), and photoacoustic imaging (PAI). Clinical and preclinical applications of NPs are identified for a broad spectrum of imaging applications, with commentaries on the future promise of these materials. Emerging technologies, for example multifunctional and theranostic NPs, and their potential for clinical advances are also discussed.
To properly assign mechanisms or causes for toxic effects of nanoscale materials, their properties and characteristics both outside and within the biological environment must be well understood. Scientists have many tools for studying the size, shape, and surface properties of particulates outside of the physiological environment; however, it is difficult to measure many of these same properties in situ without perturbing the environment, leading to spurious findings. Characterizing nanoparticle systems in situ can be further complicated by an organism's active clearance, defense, and/or immune responses. As toxicologists begin to examine nanomaterials in a systematic fashion, there is consensus that a series of guidelines or recommended practices is necessary for basic characterization of nanomaterials. These recommended practices should be developed jointly by physical scientists skilled in nano characterization and biological scientists experienced in toxicology research. In this article, basic nanoparticle characterization techniques are discussed, along with the some of the issues and implications associated with measuring nanoparticle properties and their interactions with biological systems. Recommendations regarding how best to approach nanomaterial characterization include using proper sampling and measurement techniques, forming multidisciplinary teams, and making measurements as close to the biological action point as possible.
Prior studies suggest that exposure to the natural environment may be important for optimal mental health. The present study examines the association between block-level greenness (vegetative presence) and mental health outcomes, in a population-based sample of 249,405 U.S. Medicare beneficiaries aged ≥65 years living in Miami-Dade County, Florida, USA, whose location did not change from 2010 to 2011. Multilevel analyses examined relationships between greenness, as measured by mean Normalized Difference Vegetation Index from satellite imagery at the Census block level, and each of two mental health outcomes; Alzheimer’s disease and depression, respectively, after statistically adjusting for age, gender, race/ethnicity, and neighborhood income level of the individuals. Higher block-level greenness was linked to better mental health outcomes: There was a reduced risk of Alzheimer’s disease (by 18%) and depression (by 28%) for beneficiaries living in blocks that were 1 SD above the mean for greenness, as compared to blocks that were 1 SD below the mean. Planned post-hoc analyses revealed that higher levels of greenness were associated with even greater mental health benefits in low-income neighborhoods: An increase in greenness from 1 SD below to 1 SD above the mean was associated with 37% lower odds of depression in low-income neighborhoods, compared to 27% and 21% lower odds of depression in medium- and high-income neighborhoods, respectively. Greenness may be effective in promoting mental health in older adults, particularly in low-income neighborhoods, possibly as a result of the increased opportunities for physical activity, social interaction, or stress mitigation.
We have fabricated robust nanosurgical needles suitable for single cell operations by modifying multiwalled carbon nanotube (MCNT)-terminated atomic force microscopy (AFM) tips. Extra-long MCNT AFM tips were prepared and fortified with molecular layers of carbon to overcome mechanical instabilities and then coated with an outer shell of gold to promote chemical versatility. The terminal diameters of the final fabricated tips were approximately 30-40 nm, and the MCNT probes were several micrometers in length. We illustrate the capability of these modified MCNT tips to carry nanoparticulate payloads and to penetrate the plasma membrane of living pleural mesothelial cells at the smallest indentation depths (100-200 nm) and lowest penetration forces (100-200 pN) currently reported for these procedures.
The purpose of this study was to assess the hypothesis that pain and depression negatively impact the cognitive functioning of individuals with rheumatoid arthritis (RA). One hundred twenty-one community-dwelling RA patients (ages 34-84) completed a battery of cognitive tasks and multiple measures of pain and depression. Structural equation modeling techniques were used to assess the relative contributions of pain, depression, and age to cognitive performance. Individuals who performed poorly on cognitive tasks reported more pain and depression and were older than those individuals who performed well on cognitive tasks. Moreover, high levels of pain were associated with depression. Further analyses revealed that depression mediated the relationship between pain and cognition. That is, when depression was entered into the analyses, the previously significant effects of pain on cognition were no longer found. Interestingly, depression still mediated the pain-cognition relationship even after controlling for age. These findings suggest the importance of both pain and depression for understanding cognitive function in RA and may have important implications for treating this disease.
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