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Translocation of combustion-derived particles from mother to fetus
Every single one of us is constantly exposed to polluted air, and this is not different
for pregnant women. Considering the link between prenatal air pollution exposure
and various adverse pregnancy and birth outcomes, the question arises if air
polluting particles, of which it is known that the combustion-derived fraction is
particularly harmful, can bypass the placenta to reach the fetal circulation and
organs to exert possible toxic effects. A plausible yet controversial explanation
comprises transplacental particle transfer from the mother’s lungs via maternal
blood and through the placenta to the fetal circulation. In this regard, the overall
objective of this dissertation is to unravel the ability of air polluting particles, with
a focus on combustion-derived particles (CDPs), to reach the maternal-fetal
circulation.
The key messages of each chapter discussed in this dissertation are summarised
in Table 1. First, we provide a systematic review of the existing literature on
transplacental transfer and placental-fetal accumulation of combustion-derived
(ultra)fine particles and nanoparticles (Chapter I). Here we conclude that (i) there
is sufficient experimental evidence to support the idea that combustion-derived
(ultra)fine particles and engineered nanoparticles are able to bypass the placenta
and reach the fetal circulation as observed for all applied models, irrespective of
species origin (i.e., rodent, rabbit or human) or complexity (i.e., in vitro, ex vivo or
in vivo), (ii) the majority of available studies is based on (nano)particles not related
to combustion processes despite the demonstrated toxicity of CDPs, (iii) particle
size, particle material, dose, particle dissolution, surface composition and
gestational stage of the model influence maternal-fetal translocation and (iv) no
simple, standardised method for particle detection and/or quantification in
biological samples is available to date. Given the established link between prenatal exposure to combustion-derived air
pollution and adverse birth outcomes, combined with the limited knowledge on
their transplacental transfer, the possibility of a direct fetal exposure needs to be
urgently investigated. In this dissertation, we substantiate the pathway following
direct effects on fetal development, caused by transplacental particle
translocation, by showing that CDPs, more specifically black carbon (BC) particles,
can reach the human placenta (Chapter II) under real-life exposure conditions. Ex
vivo placental perfusion with diesel exhaust particles disclosed a preferential
accumulation in the syncytiotrophoblast layer and an ability to overcome this layer
to reach the fetal capillaries (Chapter III). The presence of CDPs in human cord
blood and fetal tissues from electively terminated normally progressing
pregnancies (Chapter IV) and gestationally exposed rabbits (Chapter V) further
confirmed their transfer to the fetal circulation under real-life and controlled
exposure conditions, respectively. These findings show the ubiquity of this
environmental pollutant and prove that ambient CDPs can be transported directly
to the next generation, which may be, at least partially, responsible for the
observed detrimental health effects from early life onwards. Our findings support
direct exposure pathways, yet indirect effects should be investigated in parallel to
improve the understanding of how prenatal air pollution exposure may affect fetal
development and health in early life.
It should be noted that these results were observed in population-based studies
under real-life exposure conditions, with levels below the current European air
quality standards, (Chapters II and IV) and were unequivocally confirmed in a
controlled exposure setting (Chapters III and V). These substantial and socially
relevant findings should increase the pressure on government and individuals to
pursue action to reduce current air pollution levels even further and, with this,
protect the most vulnerable in our society, namely pregnant women
Translocation of combustion-derived particles from mother to fetus
Every single one of us is constantly exposed to polluted air, and this is not different
for pregnant women. Considering the link between prenatal air pollution exposure
and various adverse pregnancy and birth outcomes, the question arises if air
polluting particles, of which it is known that the combustion-derived fraction is
particularly harmful, can bypass the placenta to reach the fetal circulation and
organs to exert possible toxic effects. A plausible yet controversial explanation
comprises transplacental particle transfer from the mother’s lungs via maternal
blood and through the placenta to the fetal circulation. In this regard, the overall
objective of this dissertation is to unravel the ability of air polluting particles, with
a focus on combustion-derived particles (CDPs), to reach the maternal-fetal
circulation.
The key messages of each chapter discussed in this dissertation are summarised
in Table 1. First, we provide a systematic review of the existing literature on
transplacental transfer and placental-fetal accumulation of combustion-derived
(ultra)fine particles and nanoparticles (Chapter I). Here we conclude that (i) there
is sufficient experimental evidence to support the idea that combustion-derived
(ultra)fine particles and engineered nanoparticles are able to bypass the placenta
and reach the fetal circulation as observed for all applied models, irrespective of
species origin (i.e., rodent, rabbit or human) or complexity (i.e., in vitro, ex vivo or
in vivo), (ii) the majority of available studies is based on (nano)particles not related
to combustion processes despite the demonstrated toxicity of CDPs, (iii) particle
size, particle material, dose, particle dissolution, surface composition and
gestational stage of the model influence maternal-fetal translocation and (iv) no
simple, standardised method for particle detection and/or quantification in
biological samples is available to date. Given the established link between prenatal exposure to combustion-derived air
pollution and adverse birth outcomes, combined with the limited knowledge on
their transplacental transfer, the possibility of a direct fetal exposure needs to be
urgently investigated. In this dissertation, we substantiate the pathway following
direct effects on fetal development, caused by transplacental particle
translocation, by showing that CDPs, more specifically black carbon (BC) particles,
can reach the human placenta (Chapter II) under real-life exposure conditions. Ex
vivo placental perfusion with diesel exhaust particles disclosed a preferential
accumulation in the syncytiotrophoblast layer and an ability to overcome this layer
to reach the fetal capillaries (Chapter III). The presence of CDPs in human cord
blood and fetal tissues from electively terminated normally progressing
pregnancies (Chapter IV) and gestationally exposed rabbits (Chapter V) further
confirmed their transfer to the fetal circulation under real-life and controlled
exposure conditions, respectively. These findings show the ubiquity of this
environmental pollutant and prove that ambient CDPs can be transported directly
to the next generation, which may be, at least partially, responsible for the
observed detrimental health effects from early life onwards. Our findings support
direct exposure pathways, yet indirect effects should be investigated in parallel to
improve the understanding of how prenatal air pollution exposure may affect fetal
development and health in early life.
It should be noted that these results were observed in population-based studies
under real-life exposure conditions, with levels below the current European air
quality standards, (Chapters II and IV) and were unequivocally confirmed in a
controlled exposure setting (Chapters III and V). These substantial and socially
relevant findings should increase the pressure on government and individuals to
pursue action to reduce current air pollution levels even further and, with this,
protect the most vulnerable in our society, namely pregnant women
Translocation of (ultra)fine particles and nanoparticles across the placenta; a systematic review on the evidence of in vitro, ex vivo, and in vivo studies
Fetal development is a crucial window of susceptibility in which exposure may lead to detrimental health outcomes at birth and later in life. The placenta serves as a gatekeeper between mother and fetus. Knowledge regarding the barrier capacity of the placenta for nanoparticles is limited, mostly due to technical obstacles and ethical issues. We systematically summarize and discuss the current evidence and define knowledge gaps concerning the maternal-fetal transport and fetoplacental accumulation of (ultra)fine particles and nanoparticles. We included 73 studies on placental translocation of particles, of which 21 in vitro/ex vivo studies, 50 animal studies, and 2 human studies on transplacental particle transfer. This systematic review shows that (i) (ultra)fine particles and engineered nanoparticles can bypass the placenta and reach fetal units as observed for all the applied models irrespective of the species origin (i.e., rodent, rabbit, or human) or the complexity (i.e., in vitro, ex vivo, or in vivo), (ii) particle size, particle material, dose, particle dissolution, gestational stage of the model, and surface composition influence maternal-fetal translocation, and (iii) no simple, standardized method for nanoparticle detection and/or quantification in biological matrices is available to date. Existing evidence, research gaps, and perspectives of maternal-fetal particle transfer are highlighted.sponsorship: This work was supported by the Flemish Scientific Research Foundation (FWO) funding granted to EB (1150920 N), TSN and MA (G082317N), and HB (12P6819N). The FWO had no role in the design, conduct, and preparation of the manuscript. (Flemish Scientific Research Foundation (FWO)|1150920 N, Flemish Scientific Research Foundation (FWO)|G082317N, Flemish Scientific Research Foundation (FWO)|12P6819N)status: Publishe
Label-free detection of uptake, accumulation, and translocation of diesel exhaust particles in ex vivo perfused human placenta
BackgroundPregnant women and developing fetuses comprise a particularly vulnerable population as multiple studies have shown associations between prenatal air pollution exposure and adverse pregnancy outcomes. However, the mechanisms underlying the observed developmental toxicity are mostly unknown, in particular, if pollution particles can cross the human placenta to reach the fetal circulation.ResultsHere, we investigated the accumulation and translocation of diesel exhaust particles (DEPs), as a model particle for combustion-derived pollution, in human perfused placentae using label-free detection by femtosecond pulsed laser illumination. The results do not reveal a significant particle transfer across term placentae within 6 h of perfusion. However, DEPs accumulate in placental tissue, especially in the syncytiotrophoblast layer that mediates a wealth of essential functions to support and maintain a successful pregnancy. Furthermore, DEPs are found in placental macrophages and fetal endothelial cells, showing that some particles can overcome the syncytiotrophoblasts to reach the fetal capillaries. Few particles are also observed inside fetal microvessels.ConclusionsOverall, we show that DEPs accumulate in key cell types of the placental tissue and can cross the human placenta, although in limited amounts. These findings are crucial for risk assessment and protection of pregnant women and highlight the urgent need for further research on the direct and indirect placenta-mediated developmental toxicity of ambient particulates.This work received fnancial support from the Flemish Scientifc Research Foundation (Grant no 1150920N, G082317N, and 12P6819N) and the Swiss National Science Foundation (Grant no 31003A_179337 and IZSEZ0_193948). The detection equipment was funded by the Interuniversity Attraction Poles Program (P7/05) initiated by the Belgian Science Policy Ofce and the INCALO project (ERC-PoC).
Acknowledgements
The authors would like to acknowledge all participants of the study. In addition, we owe special thanks to the nurses, midwives, and doctors involved in placenta collection.The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Ambient black carbon reaches the kidneys
Background: Ultrafine particles, including black carbon (BC), can reach the systemic circulation and therefore may distribute to distant organs upon inhalation. The kidneys may be particularly vulnerable to the adverse effects of BC exposure due to their filtration function. Objectives: We hypothesized that BC particles reach the kidneys via the systemic circulation, where the particles may reside in structural components of kidney tissue and impair kidney function. Methods: In kidney biopsies from 25 transplant patients, we visualized BC particles using white light generation under femtosecond-pulsed illumination. The presence of urinary kidney injury molecule-1 (KIM-1) and cystatin c (CysC) were evaluated with ELISA. We assessed the association between internal and external exposure matrices and urinary biomarkers using Pearson correlation and linear regression models. Results: BC particles could be identified in all biopsy samples with a geometric mean (5th, 95th percentile) of 1.80 × 103 (3.65 × 102, 7.50 × 103) particles/mm3 kidney tissue, predominantly observed in the interstitium (100 %) and tubules (80 %), followed by the blood vessels and capillaries (40 %), and the glomerulus (24 %). Independent from covariates and potential confounders, we found that each 10 % higher tissue BC load resulted in 8.24 % (p = 0.03) higher urinary KIM-1. In addition, residential proximity to a major road was inversely associated with urinary CysC (+10 % distance: −4.68 %; p = 0.01) and KIM-1 (+10 % distance: −3.99 %; p < 0.01). Other urinary biomarkers, e.g., the estimated glomerular filtration rate or creatinine clearance showed no significant associations. Discussion and conclusion: Our findings that BC particles accumulate near different structural components of the kidney represent a potential mechanism explaining the detrimental effects of particle air pollution exposure on kidney function. Furthermore, urinary KIM-1 and CysC show potential as air pollution-induced kidney injury biomarkers for taking a first step in addressing the adverse effects BC might exert on kidney function
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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