Since their introduction to biological imaging, quantum dots (QDs) have progressed from a little known, but attractive technology to one that has gained broad application in many areas of biology. The versatile properties of these fluorescent nanoparticles have allowed investigators to conduct biological studies with extended spatiotemporal capabilities that were previously not possible. In this review, we focus on QD applications that provide enhanced quantitative information on protein dynamics and localization, including single particle tracking (SPT) and immunohistochemistry (IHC), and finish by examining prospects of upcoming applications, such as correlative light and electron microscopy (CLEM) and super-resolution. Advances in single molecule imaging, including multi-color and 3D QD tracking, have provided new insights into the mechanisms of cell signaling and protein trafficking. New forms of QD tracking in vivo have allowed for observation of biological processes with molecular level resolution in the physiological context of the whole animal. Further methodological development of multiplexed QD-based immunohistochemistry assays are allowing more quantitative analysis of key proteins in tissue samples. These advances highlight the unique quantitative data sets that QDs can provide to further our understanding of biological and disease processes.

The dynamics of the cellular and molecular constituents of the circulatory system are regulated by the biophysical properties of the heart, vasculature and blood cells and proteins. In this review, we discuss measurement techniques that have been developed to characterize the physical and mechanical parameters of the circulatory system across length scales ranging from the tissue scale (centimeter) to the molecular scale (nanometer) and time scales of years to milliseconds. We compare the utility of measurement techniques as a function of spatial resolution and penetration depth from both a diagnostic and research perspective. Together, this review provides an overview of the utility of measurement science techniques to study the spatial systems of the circulatory system in health and disease.

Protrusions are plasma membrane extensions that are found in almost every cell in the human body. Cancer cell filopodial and lamellipodial protrusions play key roles in the integral processes of cell motility and signaling underlying tumor invasion and metastasis. HER2 (ErbB-2) is overexpressed in diverse types of tumors and regulates PI3K-pathway-mediated protrusion growth. It is known that HER2 resides at breast cancer cell protrusions, but how protrusion-based HER2 spatiotemporal dynamics shape cancer signaling is unclear. Here, we study how HER2 location and motion regulate protrusion signaling and growth using quantitative spatio-temporal molecular imaging approaches. Our data highlight morphologically-segregated features of filopodial and lamellipodial protrusions, in in vitro 2D breast cancer cells and in vivo intact breast tumor. Functionalsegregation parallels morphological-segregation, as HER2 and its activated downstream pAKT-PI3K signaling remain spatiallylocalized at protrusions, provoking new protrusion growth proximal to sites of HER2 activation. HER2 in SKBR3 breast cancer cell filopodia exhibits fast, linearly-directed motion that is distinct from lamellipodia and non-protrusion subcellular regions (~3-4 times greater diffusion constant, rapid speeds of 2-3 um 2 /s). Surprisingly, filopodial HER2 motion is passive, requiring no active energy sources. Moreover, while HER2 motion in lamellipodia and non-protrusion regions show hindered diffusion typical of membrane proteins, HER2 diffuses freely within filopodia. We conclude that HER2 activation, propagation, and functional protrusion growth is a local process in which filopodia have evolved to exploit Brownian thermal fluctuations within a barrier-free nanostructure to transduce rapid signaling. These results support the importance of developing filopodia and other protrusion-targeted strategies for cancer.

A systematic review is conducted to identify effective interventions that improved adherence to antihypertensive drugs among patients with coronary heart diseases (CHDs). Primary studies designed to measure interventions to improve adherence on antihypertensive drugs in patients with CHD were included. Three online databases, COCHRANE, EMBASE and MEDLINE, were searched for primary studies published in English from 2005 to 2019. Studies were screened independently for eligibility. Cochrane risk-of-bias tool and the Newcastle-Ottawa Scale were used for quality assessment of randomised controlled trials (RCTs) and non-randomised studies, respectively. Of the 2000 entries identified, seven articles, including one cross-sectional study and six RCTs, met the inclusion criteria and were reviewed. One of the articles evaluated two interventions, so eight interventions were evaluated in total. Quality of the included studies was generally high, with the cross-sectional study rated as having good quality under Newcastle-Ottawa Scale, while four and two RCTs were rated as having low and some risk of bias under Cochrane risk-of-bias tool, respectively. Six of the intervention programmes were considered effective. An intervention was considered effective if it is associated with a significant (p≤0.05) and non-trivial (Cohen’s d≥0.2) improvement in compliance-related outcomes such as in terms of the Morisky 8-item Medication Adherence Scale. Medication education, disease education, health education, constant reminders and medications dispensed using blister packs were identified to be effective in improving patients’ compliance to medications. The importance of the continuity of interventions was also established. It is recommended that health service institutions should provide continuous education programmes, daily reminders and regular follow-ups for their patients who have CHD. It is recommended that further research ought to be carried out by using only one intervention in each trial with a standardised outcome measure, or using factorial designs, so that further cost-effectiveness evaluation of each intervention can be carried out independently, leading to the formulation of a comprehensive, optimised intervention programme for patients with CHD taking antihypertensives.

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