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Abstract Cathepsin D is a protease that is an effector in the immune response of macrophages, yet to date, only a limited number of probes have been developed for its detection. Herein, we report a water soluble, highly sensitive, pH insensitive fluorescent probe for the detection of Cathepsin D activity that provides a strong OFF/ON signal upon activation and with bright emission at 515 nm. The probe was synthesised using a combination of solid and solution-phase chemistries, with probe optimisation to increase its water solubility and activation kinetics by addition of a long PEG chain (5 kDa) at the C-terminus. A BODIPY fluorophore allowed detection of Cathepsin D across a wide pH range, important as the protease is active both at the low pH found in lysosomes and also in higher pH phagolysosomes, and in the cytosol. The probe was successfully used to detect Cathepsin D activity in macrophages challenged by exposure to bacteria.

Abstract Background Pancreatic adenocarcinoma (PAAD) is one of the most fatal human cancers, but effective therapies remain to be established. Cancer stem cells (CSCs) are highly resistant to anti-cancer drugs and a deeper understanding of their microenvironmental niche has been considered important to provide understanding and solutions to cancer eradication. However, as the CSC niche is composed of a wide variety of biological and physicochemical factors, the development of multidisciplinary tools that recapitulate their complex features is indispensable. Synthetic polymers have been studied as attractive biomaterials due to their tunable biofunctionalities, while hydrogelation technique further renders upon them a diversity of physical properties, making them an attractive tool for analysis of the CSC niche. Methods To develop innovative materials that recapitulate the CSC niche in pancreatic cancers, we performed polymer microarray analysis to identify niche-mimicking scaffolds that preferentially supported the growth of CSCs. The niche-mimicking activity of the identified polymers was further optimized by polyethylene glycol (PEG)-based hydrogelation. To reveal the biological mechanisms behind the activity of the optimized hydrogels towards CSCs, proteins binding onto the hydrogel were analyzed by liquid chromatography with tandem mass spectrometry (LC–MS/MS), and the potential therapeutic targets were validated by looking at gene expression and patients’ outcome in the TCGA database. Results PA531, a heteropolymer composed of 2-methoxyethyl methacrylate (MEMA) and 2-(diethylamino)ethyl methacrylate (DEAEMA) (5.5:4.5) that specifically supports the growth and maintenance of CSCs was identified by polymer microarray screening using the human PAAD cell line KLM1. The polymer PA531 was converted into five hydrogels (PA531-HG1 to HG5) and developed to give an optimized scaffold with the highest CSC niche-mimicking activities. From this polymer that recapitulated CSC binding and control, the proteins fetuin-B and angiotensinogen were identified as candidate target molecules with clinical significance due to the correlation between gene expression levels and prognosis in PAAD patients and the proteins associated with the niche-mimicking polymer. Conclusion This study screened for biofunctional polymers suitable for recapitulation of the pancreatic CSC niche and one hydrogel with high niche-mimicking abilities was successfully fabricated. Two soluble factors with clinical significance were identified as potential candidates for biomarkers and therapeutic targets in pancreatic cancers. Such a biomaterial-based approach could be a new platform in drug discovery and therapy development against CSCs, via targeting of their niche.

Photo-switching compounds are widely used as super-resolution imaging agents, anti-counterfeiting dyes, and molecules that are able to control drug–receptor interactions. However, advancement of this field has been limited by the number of classes of molecules that exhibit this phenomenon, and thus there are growing activities to discover new photo-switching compounds that diversify and improve current applications and include the so-called donor–acceptor Stenhouse adducts. Herein, a new class of compounds, phenylindole alkene dimers, are presented as a novel class of photochromic molecules that exhibit photo-switching in the solid state. The synthesis of a small library of these compounds allowed the tuning of their optical properties. Surfaces coated with these photo-switches can be used as writable materials in a variety of applications.

High data volumes from multidimensional imaging techniques can lead to slow collection and processing times. Here, the authors implement multispectral fluorescence lifetime imaging microscopy (FLIM) that uses time-correlated photon counting technology to reach simultaneously high imaging rates combined with high spectral and temporal resolution.

Ammonium group containing polymers possess inherent antimicrobial properties, effectively eliminating or preventing infections caused by harmful microorganisms. Here, homopolymers based on monomers containing ammonium groups were synthesized via Reversible Addition Fragmentation Chain Transfer Polymerization (RAFT) and evaluated as potential antibacterial agents. The antimicrobial activity was evaluated against Gram-positive (M. luteus and B. subtilis) and Gram-negative bacteria (E. coli and S. typhimurium). Three polymers, poly(diallyl dimethyl ammonium chloride), poly([2-(methacryloyloxy)ethyl]trimethylammonium chloride), and poly(vinyl benzyl trimethylammonium chloride), were examined to explore the effect of molecular weight (10 kDa, 20 kDa, and 40 kDa) on their antimicrobial activity and toxicity to mammalian cells. The mechanisms of action of the polymers were investigated with dye-based assays, while Scanning Electron Microscopy (SEM) showed collapsed and fused bacterial morphologies due to the interactions between the polymers and components of the bacterial cell envelope, with some polymers proving to be bactericidal and others bacteriostatic, while being non-hemolytic. Among all the homopolymers, the most active, non-Gram-specific polymer was poly([2-(methacryloyloxy)ethyl]trimethylammonium chloride), with a molecular weight of 40 kDa, with minimum inhibitory concentrations between 16 and 64 µg/mL, showing a bactericidal mode of action mediated by disruption of the cytoplasmic membrane. This homopolymer could be useful in biomedical applications such as surface dressings and in areas such as eye infections.

Implantable electrochemical sensors that enable the real-time detection of significant biomarkers offer huge potential for the enhancement and personalisation of therapies; however, biofouling is a key challenge encountered by any implantable system. This is particularly an issue immediately after implantation, when the foreign body response and associated biofouling processes are at their most active in passivating a foreign object. Here, we present the development of a sensor protection and activation strategy against biofouling, based on coatings consisting of a pH-triggered, dissolvable polymer, that covered a functionalised electrode surface. We demonstrate that reproducible delayed sensor activation can be achieved, and that the length of this delay can be controlled by the optimisation of coating thickness, homogeneity and density through tuning of the coating method and temperature. Comparative evaluation of the polymer-coated and uncoated probe-modified electrodes in biological media revealed significant improvements in their anti-biofouling characteristics, demonstrating that this offers a promising approach to the design of enhanced sensing devices.

The way in which photons travel through biological tissues and subsequently become scattered or absorbed is a key limitation for traditional optical medical imaging techniques using visible light. In contrast, near-infrared wavelengths, in particular those above 1000 nm, penetrate deeper in tissues and undergo less scattering and cause less photo-damage, which describes the so-called “second biological transparency window”. Unfortunately, current dyes and imaging probes have severely limited absorption profiles at such long wavelengths, and molecular engineering of novel NIR-II dyes can be a tedious and unpredictable process, which limits access to this optical window and impedes further developments. Two-photon (2P) absorption not only provides convenient access to this window by doubling the absorption wavelength of dyes, but also increases the possible resolution. This review aims to provide an update on the available 2P instrumentation and 2P luminescent materials available for optical imaging in the NIR-II window.

The development of efficient cell culture strategies for the generation of dopaminergic neurons is an important goal for transplantation-based approaches to treat Parkinson’s disease. To identify extracellular matrix molecules that enhance differentiation and might be used in these cell cultures we have used micro-contact printed arrays on glass slides presenting 190 combinations of 19 extracellular matrix molecules selected on the basis of their expression during embryonic development of the ventral midbrain. Using long-term neuroepithelial stem cells (Lt-NES), this approach identified a number of matricellular proteins that enhanced differentiation, with the combination of Sparc, Sparc-like (Sparc-l1) and Nell2 increasing the number of tyrosine hydroxylase+ neurons derived from Lt-NES cells and, critically for further translation, human pluripotent stem cells.

Abstract Population monitoring can take many different forms, and monitoring elusive and endangered species frequently involves a variety of sparse data from different sources. Small populations are often hard to sample precisely and without bias, so when estimates of vital rates like survival or recruitment point to conflicting population trends, it can be hard to determine which is more correct. Furthermore, data can be extremely hard to collect on small populations and it can be helpful to find a way to use all available hard‐won data. To address these issues, we developed an integrated population model (IPM) using all available data to estimate vital rates and abundance for a case study of an endangered woodland caribou (Rangifer tarandus caribou) population. This IPM allowed us to incorporate data from juvenile recruitment surveys, telemetry‐based survival, aerial population counts and mark–resight data, and non‐invasive capture–recapture DNA data to better understand population status and trend. We estimated survival, abundance, and recruitment of four age classes of male and female caribou: young, juveniles, subadults, and adults. The four‐age class structure of the IPM allowed us to estimate recruitment from reproductive‐aged female caribou alone, even though it can be difficult to distinguish age classes—and even sexes—in the field. As part of our IPM, we developed a novel mixture model to break apart data from different age classes when age is unobservable, as it typically is from non‐invasive DNA samples. This helped us decrease bias in juvenile and adult survival estimates from scat data, which was important to our understanding of the population dynamics. Overall, our integrated model provided more precise estimates of population trends than any one method (e.g., telemetry or non‐invasive DNA) alone. This IPM provides a useful, flexible tool for biologists to monitor populations and provides a valuable example of the benefits of integrated population modeling approaches for endangered species management and recovery.

Objective and Impact Statement. There is a need to develop platforms delineating inflammatory biology of the distal human lung. We describe a platform technology approach to detect in situ enzyme activity and observe drug inhibition in the distal human lung using a combination of matrix metalloproteinase (MMP) optical reporters, fibered confocal fluorescence microscopy (FCFM), and a bespoke delivery device. Introduction. The development of new therapeutic agents is hindered by the lack of in vivo in situ experimental methodologies that can rapidly evaluate the biological activity or drug-target engagement in patients. Methods. We optimised a novel highly quenched optical molecular reporter of enzyme activity (FIB One) and developed a translational pathway for in-human assessment. Results. We demonstrate the specificity for matrix metalloproteases (MMPs) 2, 9, and 13 and probe dequenching within physiological levels of MMPs and feasibility of imaging within whole lung models in preclinical settings. Subsequently, in a first-in-human exploratory experimental medicine study of patients with fibroproliferative lung disease, we demonstrate, through FCFM, the MMP activity in the alveolar space measured through FIB One fluorescence increase (with pharmacological inhibition). Conclusion. This translational in situ approach enables a new methodology to demonstrate active drug target effects of the distal lung and consequently may inform therapeutic drug development pathways.

The global decline in prevalence of lymphatic filariasis has been one of the major successes of the WHO's NTD programme. The recommended strategy of intensive, community-wide mass drug administration, aims to break localised transmission by either reducing the prevalence of microfilaria positive infections to below 1%, or antigen positive infections to below 2%. After the threshold is reached, and mass drug administration is stopped, geographically defined evaluation units must pass Transmission Assessment Surveys to demonstrate that transmission has been interrupted. In this study, we use an empirically parameterised stochastic transmission model to investigate the appropriateness of 1% microfilaria-positive prevalence as a stopping threshold, and statistically evaluate how well various monitoring prevalence-thresholds predict elimination or disease resurgence in the future by calculating their predictive value. Our results support the 1% filaremia prevalence target as appropriate stopping criteria. However, because at low prevalence-levels random events dominate the transmission dynamics, we find single prevalence measurements have poor predictive power for predicting resurgence, which suggests alternative criteria for restarting MDA may be beneficial.

One of the great issues for governments and related organisations everywhere is that of staying close to their citizens and maintaining accountability through the provision of accurate, trustworthy and complete information. The size of an organisation can often impede open and timely information delivery, and the complexity of government structures can cause frustration and suspicion. Given the size and complexity of the EU, it could be considered reasonable to suppose that the EU would have institutional barriers to the integrity of the information provided to the public. Indeed, criticism of the EU is frequently framed in terms of its supposed lack of accountability and the claim that it is out of touch with its citizens (Gehrke 2019). To counter this, the EU makes increasing use of online systems to render its working practices visible to the public to facilitate scrutiny and improve transparency. However, these online systems have frequently been introduced without reliable and consistent quality assurance (QA) processes to ensure the accuracy of the information in the public domain in order to promote the institutional trust that the EU seeks. Furthermore, the EU ministerial declaration of 2005 argues for promoting ‘public confidence’ in information provision for e-government. Confidence and trust are inextricably linked, as this article shows. Drawing on 22 qualitative interviews with EU officials and representatives of Civil Society Organisations (CSOs), this article demonstrates that low QA is in fact a deliberate policy, with the European Commission openly acknowledging its reliance on public control to police the information it provides through its online systems. This creates a transparency paradox by allowing CSOs to take advantage of the weakness in information QA to weaponise their information to attack the EU. This is a key consideration, not only for the EU but for all governments and non-governmental organisations across the world. A perceived weakness in information provision which subverts the building of trust, particularly political trust, increases the scope for individual or state actors to exploit the internet to weaken and undermine citizen participation. This article tackles the issue through primary research to demonstrate the dangers of weaponised information in the modern political arena.

Abstract Background This research assesses knowledge amongst drug deliverers about the implementation of mass drug administration (MDA) for lymphatic filariasis (LF) in Agam District (West Sumatera Province), the City of Depok (West Java Province) and the City of Batam (Kepulauan Riau Province), Indonesia. Methods A cross-sectional survey was conducted from January to March 2015 at these three sites. Respondents were identified using purposive sampling (i.e. cadre, health worker or community representatives). A total of 318 questionnaires were accepted for analysis. Three outcomes were assessed: knowledge about LF; knowledge about MDA implementation; and was informed about MDA coverage. Logistic regression analyses were employed to examine factors associated with these three outcomes. Results Less than half of respondents were charactersised as having a high level of LF knowledge and less than half a high level of knowledge about MDA. The odds of having a high level of knowledge of LF was significantly lower in Batam City than Agam District, yet higher amongst health workers than cadres. Deliverers living in urban areas reported more feedback on MDA outcomes than in the rural district. Health workers received more feedback than cadres (P < 0.001). Deliverers perceived the difference between coverage (drug receipt) and compliance (drug ingestion) in the community. Conclusions There are variations in knowledge about LF and MDA as well as feedback across drug deliverers in MDA across geographical areas. Adaptation of the MDA guidelines, supportive supervision, increasing the availability of supporting materials and directly-observed therapy might be beneficial to improve coverage and compliance in all areas.

Doxorubicin (Dox) is known for its potential to deliver desirable anticancer effects against various types of cancer including colorectal cancer. However, the adverse effects are serious. This study aimed to synthesize polyethylene glycol diacrylate (PEGDA)/acrylic acid (AA)-based nanoparticles (PEGDA/AA NPs) for Dox delivery to colorectal cancer cells. The NPs were synthesized using free-radical polymerization reaction using the monomers PEGDA and AA with their physical properties, drug loading and release, biocompatibility, and anticancer effect evaluated. The NPs were spherical with a size of around 230 nm, with a 48% Dox loading efficiency and with loading capacity of 150 µg/mg. Intriguingly, the NPs had the ability to prolong the release of Dox in vitro over 24 h and were non-toxic to intestinal epithelial cells. Dox-loaded PEGDA/AA NPs (Dox-NPs) were able to effectively kill the colorectal cancer cell line (HT-29) with the Dox-NPs accumulating inside the cell and killing the cell through the apoptosis pathway. Overall, the synthesized PEGDA/AA NPs exhibit considerable potential as a drug delivery carrier for colon cancer-directed, staged-release therapy.

Colour is about more than just lightwaves hitting the retina. In ancient philosophical circles, colour was described as the primary object of vision: it was the external ‘skin’ that existed at the surface of an object, and what made the object visible or ‘sensible’ to a viewer. And yet, Greco-Roman literature is riddled with examples of colour categories that do not make sense simply in visual terms: from Homer’s ‘wine-dark sea’ (oinops pontos) to ‘whey-coloured’ (orōdēs) skin in Hippocratic medicine, from blushing (rubens) faces to the honey-coloured hair (mellei crines) and marbled skin of coveted girls in Augustan elegy, and from the saffron garments of decadent easterners to the expensive fishy-smelling purple robes of the late-antique imperial court, colours appealed not just to sight, but also to smell, touch and taste. This paper will use arguments and ideas explored in my monograph Colour and Meaning in Ancient Rome (Cambridge University Press, 2009) to suggest that colours in pre-modern societies such as Greece and Rome, because of their close ties to specific objects and phenomena (rather than just parts of the spectrum), were frequently synaesthetic experiences which appealed to multiple senses and mobilized more than just eyesight. I will draw upon case studies from a range of genres and contexts to demonstrate not only that colour was a multi-sensory experience, but also that the nature of this experience was a central preoccupation of ancient thought in several areas of activity in the Greco-Roman world. An understanding of this principle, then, can do more than just help us to translate and understand difficult Greek and Latin colour terms: colour was a basic sensory unit of information through which ancients experienced and evaluated the world around them, and the collaboration of the senses in these experiences suggests an approach to perception, knowledge and understanding which could be very different from that employed in the modern west.

Abstract Background Lymphatic filariasis (LF) occurs when filarial parasites are transmitted to humans through mosquitoes. The filarial worms affect the lymphatic system which leads to abnormal enlargement of body parts, chronic pain, disability, and social discrimination. In 1999, a commitment was made to eliminate LF from the Pacific Region by 2010. The Pacific Program to Eliminate LF began, with Vanuatu being one of the 16 endemic countries included in this program. Methods In 1997/1998 a LF prevalence baseline survey was conducted to determine the need for mass drug administration (MDA) in Vanuatu. In 1999, the Vanuatu Lymphatic Filariasis Control Program was established, and nationwide MDA was implemented from 2000 to 2004. LF prevalence was collected during the MDA through sentinel site and spot check surveys, and after 5 years of MDA. MDA implementation methods included health worker training, social mobilization, and culturally appropriate health promotion strategies. Results LF prevalence at baseline was 4.79%; after MDA this declined to 0.16% in 2005/2006. Average MDA coverage ranged from 75.5–81.5% across 5 years. All three evaluation units surveyed in 2005/2006 were below the 1% threshold required to stop MDA. Conclusions The LF Control Program between 1997 and 2006 was successful in reducing LF prevalence to

Abstract Decellularized vascular scaffolds are promising materials for vessel replacements. However, despite the natural origin of decellularized vessels, issues such as biomechanical incompatibility, immunogenicity risks and the hazards of thrombus formation, still need to be addressed. In this study, we coated decellularized vessels obtained from porcine carotid arteries with poly (ethylmethacrylate-co-diethylaminoethylacrylate) (8g7) with the purpose of improving endothelial coverage and minimizing platelet attachment while enhancing the mechanical properties of the decellularized vascular scaffolds. The polymer facilitated binding of endothelial cells (ECs) with high affinity and also induced endothelial cell capillary tube formation. In addition, platelets showed reduced adhesion on the polymer under flow conditions. Moreover, the coating of the decellularized arteries improved biomechanical properties by increasing its tensile strength and load. In addition, after 5 days in culture, ECs seeded on the luminal surface of 8g7-coated decellularized arteries showed good regeneration of the endothelium. Overall, this study shows that polymer coating of decellularized vessels provides a new strategy to improve re-endothelialization of vascular grafts, maintaining or enhancing mechanical properties while reducing the risk of thrombogenesis. These results could have potential applications in improving tissue-engineered vascular grafts for cardiovascular therapies with small caliber vessels.

The optical molecular imaging of inflammation is an emerging strategy for interventional medicine and diagnostics. The host's inflammatory response and adaptation to acute and chronic diseases provides unique signatures that have the potential to guide interventions. Thus, there are emerging a suite of molecular imaging and sensing approaches for a variety of targets in this area. This review will focus on two key cellular orchestrators that dominate this area, neutrophils and macrophages, with recent developments in molecular probes and approaches discussed.

Two novel, water-soluble, merocyanine fluorophores were readily prepared by microwave-assisted synthesis. Full optical characterization was performed in a series of protic and aprotic solvents, and the dyes displayed fluorescence in the red region with up to a 20-fold decrease in brightness in water, demonstrating a strong environmental sensitivity hereby termed as solvato-fluorogenicity (to distinguish from solvatochromism). Shorter fluorescent lifetimes were also measured in water, which confirmed this character. These dyes were conjugated to a modified polymyxin scaffold that allowed fluorescence “switch-on” upon binding to Gram-negative bacterial membranes, and selective fluorescence detection of bacteria in a wash-free protocol.

The cellular plasma membrane plays a fundamental role in biological processes, including cell growth, signaling and transport. The labelling of the plasma membrane with targeted fluorescent probes offers a convenient and non-invasive way to image the morphological changes and dynamics of a membrane in real-time and, despite many examples of fluorescent plasma membrane probes, a “universal targeting/anchoring moiety” is still required. In this study, a small number of stearic acid-based probes labelled with 6-carboxyfluorescein was designed and fabricated via solid-phase synthesis in which variations in both charge and hydrophobicity were explored. To ease the synthesis process, a gram-scale synthesis of the Fmoc-Lys(6-carboxyfluoresein diacetate)-OH building block was developed, allowing the discovery of optimal probes that carried a positively charged amino group and a stearic acid tail that exhibited intense plasma membrane brightness and robust retention.

Photodynamic inactivation of microorganisms has gained substantial attention due to its unique mode of action, in which pathogens are unable to generate resistance, and due to the fact that it can be applied in a minimally invasive manner. In photodynamic therapy (PDT), a non-toxic photosensitizer (PS) is activated by a specific wavelength of light and generates highly cytotoxic reactive oxygen species (ROS) such as superoxide (O2−, type-I mechanism) or singlet oxygen (1O2*, type-II mechanism). Although it offers many advantages over conventional treatment methods, ROS-mediated microbial killing is often faced with the issues of accessibility, poor selectivity and off-target damage. Thus, several strategies have been employed to develop target-specific antimicrobial PDT (aPDT). This includes conjugation of known PS building-blocks to either non-specific cationic moieties or target-specific antibiotics and antimicrobial peptides, or combining them with targeting nanomaterials. In this review, we summarise these general strategies and related challenges, and highlight recent developments in targeted aPDT.

Numerous optodes, with fluorophores as the chemical sensing element and optical fibres for light delivery and collection, have been fabricated for minimally invasive endoscopic measurements of key physiological parameters such as pH. These flexible miniaturised optodes have typically attempted to maximize signal-to-noise through the application of high concentrations of fluorophores. We show that high-density attachment of carboxyfluorescein onto silica microspheres, the sensing elements, results in fluorescence energy transfer, manifesting as reduced fluorescence intensity and lifetime in addition to spectral changes. We demonstrate that the change in fluorescence intensity of carboxyfluorescein with pH in this “high-density” regime is opposite to that normally observed, with complex variations in fluorescent lifetime across the emission spectra of coupled fluorophores. Improved understanding of such highly loaded sensor beads is important because it leads to large increases in photostability and will aid the development of compact fibre probes, suitable for clinical applications. The time-resolved spectral measurement techniques presented here can be further applied to similar studies of other optodes.

Small and declining populations of large mammals are vulnerable to stochastic events and can be at high risk of extinction. Population viability is also susceptible to the detrimental effects of low genetic diversity and inbreeding. The objective of this study was to do an assessment of three endangered caribou subpopulations using non-invasive genetic sampling to assess demographic population changes by combining capture-recapture modeling, familial pedigree networks, individual fitness and inbreeding coefficients. Three subpopulations of the Central Mountain caribou ecotype (Rangifer tarandus caribou) in Jasper National Park, Canada, were systematically surveyed over a 10-year period and fecal samples collected for DNA analyses. For the Tonquin, population size declined at a rate of 0.86 (95% CI 0.82, 0.91), the number of females decreased from 41 in 2006 to only 14 in 2015. The Brazeau and Maligne subpopulations also declined over the same period, from 22 to 11 individuals (11 and 5 females) in 2006, to 12 and 3 individuals (6 and 1 females) in 2015. The pedigree network confirmed limited interbreeding among subpopulations, varied fitness levels in both males and females, and evidence of inbreeding avoidance among high-fitness individuals. All population parameters pointed to a rapid population decline and low population sizes, putting them at high risk of extinction. The varying reproductive fitness observed amongst males and females was significant and should be considered in future population augmentation or reintroduction efforts. Improved connectivity among and with neighbouring subpopulations should also be considered to sustain or enhance genetic diversity. Keywords: Conservation genetics, Pedigrees, Inbreeding, Non-invasive genetic sampling, Rangifer tarandus, Varied fitness

BACKGROUND:As the Global Programme to Eliminate Lymphatic Filariasis (LF) approaches its 2020 goal, an increasing number of districts will enter the endgame phase where drug coverage rates from mass drug administration (MDA) are used to assess whether MDA can be stopped. As reported, the gap between reported and actual drug coverage in some contexts has overestimated the true rates, thus causing premature administration of transmission assessment surveys (TAS) that detect ongoing LF transmission. In these cases, districts must continue with additional rounds of MDA. Two districts in Indonesia (Agam District, Depok City) fit this criteria-one had not met the pre-TAS criteria and the other, had not passed the TAS criteria. In both cases, the district health teams needed insight into their drug delivery programs in order to improve drug coverage in the subsequent MDA rounds. METHODOLOGY/PRINCIPAL FINDINGS:To inform the subsequent MDA round, a micronarrative survey tool was developed to capture community members' experience with MDA and the social realm where drug delivery and compliance occur. A baseline survey was implemented after the 2013 MDA in endemic communities in both districts using the EPI sampling criteria (n = 806). Compliance in the last MDA was associated with perceived importance of the LF drugs for health (p

This manuscript describes the use of a novel biochip platform for the rapid analysis/identification of nucleic acids, including DNA and microRNAs, with very high specificity. This approach combines a unique dynamic chemistry approach for nucleic acid testing and analysis developed by DestiNA Genomics with the STMicroelectronics In-Check platform, which comprises two microfluidic optimized and independent PCR reaction chambers, and a sequential microarray area for nucleic acid capture and identification by fluorescence. With its compact bench-top “footprint” requiring only a single technician to operate, the biochip system promises to transform and expand routine clinical diagnostic testing and screening for genetic diseases, cancers, drug toxicology and heart disease, as well as employment in the emerging companion diagnostics market.

The evaluation of the role of physicochemical properties in the toxicity of nanoparticles is important for the understanding of toxicity mechanisms and for controlling the behavior of nanoparticles. The surface charge of nanoparticles is suggested as one of the key parameters which decide their biological impact. In this study, we synthesized fluorophore-conjugated polystyrene nanoparticles (F-PLNPs), with seven different types of surface functional groups that were all based on an identical core, to evaluate the role of surface charge in the cellular uptake of nanoparticles. Phagocytic differentiated THP-1 cells or non-phagocytic A549 cells were incubated with F-PLNP for 4 h, and their cellular uptake was quantified by fluorescence intensity and confocal microscopy. The amount of internalized F-PLNPs showed a good positive correlation with the zeta potential of F-PLNPs in both cell lines (Pearson’s r = 0.7021 and 0.7852 for zeta potential vs. cellular uptake in THP-1 cells and nonphagocytic A549 cells, respectively). This result implies that surface charge is the major parameter determining cellular uptake efficiency, although other factors such as aggregation/agglomeration, protein corona formation, and compositional elements can also influence the cellular uptake partly or indirectly.