Background/Aims: Endometriosis has a long diagnostic delay that is influenced by varying socio-economic and healthcare factors. In the Dutch situation, these factors are not yet identified. The aim of this study is to determine the length of the diagnostic delay of endometriosis in the Netherlands and to identify which variables affect this delay. Methods: A retrospective study among 139 patients diagnosed with endometriosis in a secondary care hospital with a specialized multidisciplinary endometriosis team. The diagnostic process was evaluated using a questionnaire-guided telephonic interview. Results: The median time interval from the onset of symptoms to diagnosis was 89 months or 7.4 years, divided in 7 months patient delay, 35 months general practitioner (GP) delay and 5 months gynecologist delay. Determinants for a longer diagnostic delay were young age at onset of symptoms, use of oral contraceptives or analgesics prescribed by GP, alternative diagnoses considered by the GP, and cyclic symptoms. Subfertility as presenting symptom resulted in faster diagnosis. Conclusion: This study shows that the time interval to the diagnosis of endometriosis is long and mainly consists of the period of time the woman consults her first line medical professional.
Photoacoustic imaging (PAI) is an emerging biomedical imaging technique that is now coming to the clinic. It has a penetration depth of a few centimeters and generates useful endogenous contrast, particularly from melanin and oxy-/deoxyhemoglobin. Indocyanine green (ICG) is a Food and Drug Administration-approved contrast agents for human applications, which can be also used in PAI. It is a small molecule dye with limited applications due to its fast clearance, rapid protein binding, and bleaching effect.Methods: Here, we entrap ICG in a poly(lactic-co-glycolic acid) nanoparticles together with a perfluorocarbon (PFC) using single emulsion method. These nanoparticles and nanoparticle-loaded dendritic cells were imaged with PA, 19F MR, and fluorescence imaging in vitro and in vivo.Results: We formulated particles with an average diameter of 200 nm. The encapsulation of ICG within nanoparticles decreased its photobleaching and increased the retention of the signal within cells, making it available for applications such as cell imaging. As little as 0.1x106 cells could be detected in vivo with PAI using automated spectral unmixing. Furthermore, we observed the accumulation of ICG signal in the lymph node after subcutaneous injection of nanoparticles.Conclusion: We show that we can label primary human dendritic cells with the nanoparticles and image them in vitro and in vivo, in a multimodal manner. This work demonstrates the potential of combining PAI and 19F MRI for cell imaging and lymph node detection using nanoparticles that are currently produced at GMP-grade for clinical use.
Neutrophils kill ingested pathogens by the so-called oxidative burst, where reactive oxygen species (ROS) are produced in the lumen of phagosomes at very high rates (mM/s), although these rates can only be maintained for a short period (minutes). In contrast, dendritic cells produce ROS at much lower rates, but they can sustain production for much longer after pathogen uptake (hours). It is becoming increasingly clear that this slow but prolonged ROS production is essential for antigen cross-presentation to activate cytolytic T cells, and for shaping the repertoire of antigen fragments for presentation to helper T cells. However, despite this importance of ROS production by dendritic cells for activation of the adaptive immune system, their actual ROS production rates have never been quantified. Here, we quantified ROS production in human monocyte-derived dendritic cells by measuring the oxygen consumption rate during phagocytosis. Although a large variation in oxygen consumption and phagocytic capacity was present among individuals and cells, we estimate a ROS production rate of on average ~0.5 mM/s per phagosome. Quantitative microscopy approaches showed that ROS is produced within minutes after pathogen encounter at the nascent phagocytic cup. H
2
DCFDA measurements revealed that ROS production is sustained for at least ~10 h after uptake. While ROS are produced by dendritic cells at an about 10-fold lower rate than by neutrophils, the net total ROS production is approximately similar. These are the first quantitative estimates of ROS production by a cell capable of antigen cross-presentation. Our findings provide a quantitative insight in how ROS affect dendritic cell function.
Spraying of agrochemicals (pesticides, fertilizers) causes environmental pollution on a million‐ton scale. A sustainable alternative is target‐specific, on‐demand drug delivery by polymeric nanocarriers. Trunk injections of aqueous nanocarrier dispersions can overcome the biological size barriers of roots and leaves and allow distributing the nanocarriers through the plant. To date, the fate of polymeric nanocarriers inside a plant is widely unknown. Here, the in planta conditions in grapevine plants are simulated and the colloidal stability of a systematic series of nanocarriers composed of polystyrene (well‐defined model) and biodegradable lignin and polylactic‐co‐glycolic acid by a combination of different techniques is studied. Despite the adsorption of carbohydrates and other biomolecules onto the nanocarriers’ surface, they remain colloidally stable after incubation in biological fluids (wood sap), suggesting a potential transport via the xylem. The transport is tracked by fluorine‐ and ruthenium‐labeled nanocarriers inside of grapevines by 19F‐magnetic resonance imaging or induced coupled plasma – optical emission spectroscopy. Both methods show that the nanocarriers are transported inside of the plant and proved to be powerful tools to localize nanomaterials in plants. This study provides essential information to design nanocarriers for agrochemical delivery in plants to sustainable crop protection.
Perfluorocarbon-loaded
nanoparticles are powerful theranostic agents, which are used in the
therapy of cancer and stroke and as imaging agents for ultrasound
and
19
F magnetic resonance imaging (MRI). Scaling up the
production of perfluorocarbon-loaded nanoparticles is essential for
clinical translation. However, it represents a major challenge as
perfluorocarbons are hydrophobic and lipophobic. We developed a method
for continuous-flow production of perfluorocarbon-loaded poly(lactic-
co
-glycolic acid) (PLGA) nanoparticles using a modular microfluidic
system, with sufficient yields for clinical use. We combined two slit
interdigital micromixers with a sonication flow cell to achieve efficient
mixing of three phases: liquid perfluorocarbon, PLGA in organic solvent,
and aqueous surfactant solution. The production rate was at least
30 times higher than with the conventional formulation. The characteristics
of nanoparticles can be adjusted by changing the flow rates and type
of solvent, resulting in a high PFC loading of 20–60 wt % and
radii below 200 nm. The nanoparticles are nontoxic, suitable for
19
F MRI and ultrasound imaging, and can dissolve oxygen.
In vivo
19
F MRI with perfluoro-15-crown-5 ether-loaded
nanoparticles showed similar biodistribution as nanoparticles made
with the conventional method and a fast clearance from the organs.
Overall, we developed a continuous, modular method for scaled-up production
of perfluorocarbon-loaded nanoparticles that can be potentially adapted
for the production of other multiphase systems. Thus, it will facilitate
the clinical translation of theranostic agents in the future.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.