T cell migration and effector function differences in familial adenomatous polyposis patients with APC gene mutations.

Familial adenomatous polyposis (FAP) is an inherited disease characterized by the development of large number of colorectal adenomas with high risk of evolving into colorectal tumors. Mutations of the Adenomatous polyposis coli (APC) gene is often at the origin of this disease, as well as of a high percentage of spontaneous colorectal tumors. APC is therefore considered a tumor suppressor gene. While the role of APC in intestinal epithelium homeostasis is well characterized, its importance in immune responses remains ill defined. Our recent work indicates that the APC protein is involved in various phases of both CD4 and CD8 T cells responses. This prompted us to investigate an array of immune cell features in FAP subjects carrying APC mutations. A group of 12 FAP subjects and age and sex-matched healthy controls were studied. We characterized the immune cell repertoire in peripheral blood and the capacity of immune cells to respond ex vivo to different stimuli either in whole blood or in purified T cells. A variety of experimental approaches were used, including, pultiparamater flow cytometry, NanosString gene expression profiling, Multiplex and regular ELISA, confocal microscopy and computer-based image analyis methods. We found that the percentage of several T and natural killer (NK) cell populations, the expression of several genes induced upon innate or adaptive immune stimulation and the production of several cytokines and chemokines was different. Moreover, the capacity of T cells to migrate in response to chemokine was consistently altered. Finally, immunological synapses between FAP cytotoxic T cells and tumor target cells were more poorly structured. Our findings of this pilot study suggest that mild but multiple immune cell dysfunctions, together with intestinal epithelial dysplasia in FAP subjects, may facilitate the long-term polyposis and colorectal tumor development. Although at an initial discovery phase due to the limited sample size of this rare disease cohort, our findings open new perspectives to consider immune cell abnormalities into polyposis pathology.

Towards digital healthy ageing: the case of Agatha and priorities moving forward.

Digital tools have an important role to play in meeting the health demands of ageing societies. However, current technological design paradigms often marginalize older people. We adopted a lean, user-centred approach to prototype the Avatar for Global Access to Technology for Healthy Ageing (Agatha), an interactive one-stop shop for healthy ageing promotion. Building on this experience, we present a vision for an integrated approach to "digital healthy ageing". Older people consulted predominantly associated "healthy ageing" with disease avoidance. Digital healthy ageing should take a more holistic approach, covering self-care, prevention, and active ageing. It should also consider social determinants of health in old age, including access to information and digital health literacy, as they interact with poverty, education, access to health services and other structural factors. We use this framework to map out key areas of innovation and explore policy priorities and opportunities for innovation practitioners.

Foresight in the time of COVID-19.

Foresight methodologies enable individuals and organizations to envision different future scenarios and plan for greater future resilience. However, foresight is an underused methodology in the Western Pacific region for health policy development that could be extremely beneficial, among other areas, in the context of public health emergency response. We present lessons learned from the application of foresight methodologies through remote, agile think tank sprints to inform the World Health Organization (WHO) Western Pacific Regional Office's (WPRO) response to the COVID-19 pandemic. Four think tanks were set up in topic areas of interest. The think tanks used a six-step foresight methodology to develop scenarios for the pandemic in an 18-month horizon. Backcasting was used to generate recommendations for WHO response and support for countries. This case study demonstrates the value of using foresight methodologies in public health, and specifically in the context of a public health emergency, and its ability to inform more context-appropriate and future-proof responses. FUNDING: Japan.

An assessment of the quality of vaccination data produced through smart paper technology in The Gambia.

INTRODUCTION: MyChild Solution is an innovative Electronic Immunisation Register (EIR) reliant on Smart Paper Technology, thereby eliminating the need for electronic devices and internet connectivity at the point-of-care. The goal of this study is to characterise the quality of routine immunisation data generated using MyChild Solution compared to data obtained through the conventional health management information system (HMIS) used in The Gambia. METHOD: We used the World Health Organization's (WHO) Data Quality Review (DQR) Toolkit to evaluate MyChild Solution's data quality in the 19 health facilities across two regions implementing MyChild Solution in The Gambia at the time of the evaluation. We evaluated all applicable data quality metrics as well as additional metrics of interest, including the incidence of recording errors, the incidence of incomplete indicator level data, and implausible dates. Where possible, we compared results to those of the conventional HMIS. RESULTS: Both MyChild Solution and the conventional HMIS produced 100% complete and timely data in their reference years. Both systems had no moderate or extreme outliers and showed the expected Penta 1 to Penta 3 dropout direction. However, the proportion of verification factors that are not acceptable was higher in the conventional HMIS. MyChild Solution was found to near perfectly (99.98%) digitise scanned documents. These and other data quality indicators evaluated demonstrate that MyChild Solution produces high quality data with high completeness, timeliness, and consistency compared to the conventional HMIS system. CONCLUSION: MyChild Solution produces high quality data as per the DQR Toolkit metrics and other metrics of interest of interest. The more internally consitent data produced through MyChild Solution compared to the conventional HMIS demonstrates its potential for supporting data-driven decision-making in immunisation.

Engineering vasculature: Architectural effects on microcapillary-like structure self-assembly.

One of the greatest obstacles to clinical translation of bone tissue engineering is the inability to effectively and efficiently vascularize scaffolds. The goal of this work was to explore systematically whether architecture, at a scale of hundreds of microns, can be used to direct the growth of microcapillary-like structures into the core of scaffolds. Biphasic bioceramic patterned architectures were produced using silicone molds of 3D printed parts. Grooves and ridges were designed to have widths of 330 µm and 660 µm, with periodicities respectively of 1240 µm and 630 µm. Groove depth was varied between 150 µm and 585 µm. Co-cultures of human dermal microvascular endothelial cells (HDMECs) and human osteoblasts (hOBs) were used to grow microcapillary-like structures on substrates. Bioceramic architecture was found to significantly affect microcapillary-like structure location and orientation. Microcapillary-like structures were found to form predominantly in grooves or between convexities. For all patterned samples, the CD31 (endothelial cell marker) signal was at least 2.5 times higher along grooves versus perpendicular to grooves. In addition, the average signal was at least two times higher within grooves than outside grooves for all samples. Grooves with a width of 330 µm and a depth of 300 µm resulted in the formation of individual, highly aligned microcapillary-like structures with lengths around 5 mm. Extensive literature has focused on the role of nano- and micro-topography (on the scale below tens of microns) on cellular response. However, the idea that architecture at a scale much larger than a cell could be used to modulate angiogenesis has not been systematically investigated. This work shows the crucial influence of architecture on microcapillary-like structure self-assembly at the scale of hundreds of microns. Elucidating the precise correspondence between architecture and microcapillary-like structure organization will ultimately allow the engineering of microvasculature by tuning local scaffold design to achieve desirable microvessel properties.

3D Printed Multimaterial Microfluidic Valve.

We present a novel 3D printed multimaterial microfluidic proportional valve. The microfluidic valve is a fundamental primitive that enables the development of programmable, automated devices for controlling fluids in a precise manner. We discuss valve characterization results, as well as exploratory design variations in channel width, membrane thickness, and membrane stiffness. Compared to previous single material 3D printed valves that are stiff, these printed valves constrain fluidic deformation spatially, through combinations of stiff and flexible materials, to enable intricate geometries in an actuated, functionally graded device. Research presented marks a shift towards 3D printing multi-property programmable fluidic devices in a single step, in which integrated multimaterial valves can be used to control complex fluidic reactions for a variety of applications, including DNA assembly and analysis, continuous sampling and sensing, and soft robotics.

Effect of Ceramic Scaffold Architectural Parameters on Biological Response.

Numerous studies have focused on the optimization of ceramic architectures to fulfill a variety of scaffold functional requirements and improve biological response. Conventional fabrication techniques, however, do not allow for the production of geometrically controlled, reproducible structures and often fail to allow the independent variation of individual geometric parameters. Current developments in additive manufacturing technologies suggest that 3D printing will allow a more controlled and systematic exploration of scaffold architectures. This more direct translation of design into structure requires a pipeline for design-driven optimization. A theoretical framework for systematic design and evaluation of architectural parameters on biological response is presented. Four levels of architecture are considered, namely (1) surface topography, (2) pore size and geometry, (3) porous networks, and (4) macroscopic pore arrangement, including the potential for spatially varied architectures. Studies exploring the effect of various parameters within these levels are reviewed. This framework will hopefully allow uncovering of new relationships between architecture and biological response in a more systematic way as well as inform future refinement of fabrication techniques to fulfill architectural necessities with a consideration of biological implications.