Theranostic Gold Nanoantennas for Simultaneous Multiplexed Raman Imaging of Immunomarkers and Photothermal Therapy.

In this study, we demonstrate the theranostic capability of actively targeted, site-specific multibranched gold nanoantennas (MGNs) in triple-negative breast cancer (TNBC) cells in vitro. By utilizing multiplexed surface-enhanced Raman scattering (SERS) imaging, enabled by the narrow peak widths of Raman signatures, we simultaneously targeted immune checkpoint receptor programmed death ligand 1 (PDL1) and the epidermal growth factor receptor (EGFR) overexpressed in TNBC cells. A 1:1 mixture of MGNs functionalized with anti-PDL1 antibodies and Raman tag 5,5-dithio-bis-(2-nitrobenzoic acid) (DTNB) and MGNs functionalized with anti-EGFR antibodies and Raman tag para-mercaptobenzoic acid (pMBA) were incubated with the cells. SERS imaging revealed a cellular traffic map of MGN localization by surface binding and receptor-mediated endocytosis, enabling targeted diagnosis of both biomarkers. Furthermore, cells incubated with anti-EGFR-pMBA-MGNs and illuminated with an 808 nm laser for 15 min at 4.7 W/cm2 exhibited photothermal cell death only within the laser spot (indicated by live/dead cell fluorescence assay). Therefore, this study not only provides an optical imaging platform that can track immunomarkers with spatiotemporal control but also demonstrates an externally controlled light-triggered therapeutic approach enabling receptor-specific treatment with biocompatible theranostic nanoprobes.

Gold Nanoantenna-Mediated Photothermal Drug Delivery from Thermosensitive Liposomes in Breast Cancer.

In this work, we demonstrate controlled drug delivery from low-temperature-sensitive liposomes (LTSLs) mediated by photothermal heating from multibranched gold nanoantennas (MGNs) in triple-negative breast cancer (TNBC) cells in vitro. The unique geometry of MGNs enables the generation of mild hyperthermia (∼42 °C) by converting near-infrared light to heat and effectively delivering doxorubicin (DOX) from the LTSLs in breast cancer cells. We confirmed the cellular uptake of MGNs by using both fluorescence confocal Z-stack imaging and transmission electron microscopy (TEM) imaging. We performed a cellular viability assay and live/dead cell fluorescence imaging of the combined therapeutic effects of MGNs with DOX-loaded LTSLs (DOX-LTSLs) and compared them with free DOX and DOX-loaded non-temperature-sensitive liposomes (DOX-NTSLs). Imaging of fluorescent live/dead cell indicators and MTT assay outcomes both demonstrated significant decreases in cellular viability when cells were treated with the combination therapy. Because of the high phase-transition temperature of NTSLs, no drug delivery was observed from the DOX-NTSLs. Notably, even at a low DOX concentration of 0.5 µg/mL, the combination treatment resulted in a higher (33%) cell death relative to free DOX (17% cell death). The results of our work demonstrate that the synergistic therapeutic effect of photothermal hyperthermia of MGNs with drug delivery from the LTSLs can successfully eradicate aggressive breast cancer cells with higher efficacy than free DOX by providing a controlled light-activated approach and minimizing off-target toxicity.

Social participation of teenagers and young adults with developmental co-ordination disorder and strategies that could help them: results from a scoping review.

BACKGROUND: The impact of developmental co-ordination disorder (DCD) on teenagers' and young adults' participation is not well documented. This article aims to synthesize the current knowledge on social participation, which is the performance of an individual in realizing his or her daily activities and social roles within its life environment. Strategies and interventions to support youths (15-25 years old) with DCD were also synthesized. METHODS: A scoping review interrogating three databases and using 'snowballing techniques' was performed to identify both scientific and grey literature published between 2004 and 2014. Over 1000 documents were screened and 57 were read in full; 28 met inclusion criteria. A charting form based on 12 life habits described in the disability creation process and developed by two reviewers was used to extract data and report the results. RESULTS: All life habits were reported to be affected for teenagers and young adults with DCD, with education and interpersonal relationships being the most frequently discussed. During adolescence and adulthood, new tasks and subsequent difficulties emerge, such as driving. Mental health difficulties emerged as a key theme. Few strategies and interventions were described to support social participation of youths with DCD. CONCLUSION: Many life habits are challenging for youths with DCD, but few evidence-based strategies and interventions have been designed to help them to increase their social participation.

Best practice principles for management of children with developmental coordination disorder (DCD): results of a scoping review.

BACKGROUND: Developmental coordination disorder (DCD) is a prevalent health condition that is frequently unrecognized despite the substantial evidence that has accumulated regarding how it affects children's health, education and skills. Most literature focuses on measurement of impairment and description of intervention approaches for individual children; little is known about the principles that should guide best practice and service delivery for children with DCD as a population. The purpose of this study was to identify these principles. METHODS: A scoping review was used to 'map' the information available to inform intervention and service delivery. Scholarly and grey literature written in English was identified in six databases, using a combination of keywords (e.g. guidelines, management, models and DCD); a 'snow-balling' technique was also used in Canada and the UK to access clinical protocols used in publicly funded health care systems. Over 500 documents were screened: 31 met inclusion criteria as they outlined practice principles for children with DCD as a population. Data regarding best practices were independently extracted by two reviewers and then compared with achieve consistency and consensus. RESULTS: Two over-arching themes emerged, with five principles: (1) Organizing services to efficiently meet the comprehensive needs of children (e.g. Increasing awareness of DCD and coordination; Implementing clearly defined pathways; Using a graduated/staged approach); (2) Working collaboratively to offer evidence-based services (e.g. Integration of child and family views; Evidence-based interventions fostering function, participation and prevention). CONCLUSION: Numerous documents support each of the principles, reflecting agreement across studies about recommended organization of services. While these principles may apply to many populations of children with disabilities, this review highlights how essential these principles are in DCD. Researchers, managers, clinicians, community partners and families are encouraged to work together in designing, implementing and evaluating interventions that reflect these principles.

An approach to improving hospital advertising.

Newspaper ads from hospitals in Ohio were rated for their effectiveness and explicit use of marketing principles. Analysis showed that the advertising could be improved by increasing the motivation for action, emphasizing how the organization's products and services are different from competitors and more thoroughly identifying the benefits the consumer would receive. Use of the two forms in the study can contribute to improved health care advertising.

Congruity and predictability between two measures of nonstandard dialect usage on four grammatical forms.

This study investigated whether Nonstandard English (NSE) dialect responses to an examiner-constructed sentence completion test were congruent with and predictive of use of NSE during spontaneous conversation. The sentence completion test was designed to evoke either NSE or Standard English (SE) dialect variants of four grammatical forms for which the NSE dialect variants are highly stigmatized. The 76 Black male subjects were between the ages of 15:8 and 23:5 years. The grammatical forms assessed were verb-subject agreement third person singular, negative concord, possessive suffix, and continuative be. A low but statistically significant correlation was found between the percentage of NSE usage on the test and during conversation when all four grammatical forms were combined (r = .2344, p less than .05). Only the possessive suffix form showed a statistically significant correlation between the two measures when correlations were computed for individual grammatical forms (r = .4341, p less than .05). Thus, congruency was interpreted to be highly variable and dependent on the particular grammatical form. To measure predictability, data were inspected for each grammatical form to determine the percentage of subjects who used at least one NSE dialect variant for sentence completion test items when at least one NSE variant of that form occurred during spontaneous conversation. Responses to the sentence completion test were predictive of NSE during conversation for more than 90% of the subjects only for the negative concord grammatical form. It was concluded that the sentence completion test is satisfactorily congruent with and predictive of patterns of dialect used in spontaneous conversation only for certain specific grammatical forms. Some possible reasons for these variable results and their implications for second dialect assessment are offered.