Consumption of freshwater fish: A variable but significant risk factor for PFOS exposure

PFOS, PFOA, PFNA and PFHxS are the PFAS substances that currently contribute most to human exposure, and in 2020 the European Food Safety Authority (EFSA) presented a draft opinion on a tolerable intake of 8 ng/kg/week for the sum of these four substances (equaling 0.42 mu g/kg if expressed as an annual dose). Diet is usually the dominating exposure pathway, and in particular the intake of PFOS has been shown to be strongly related to the consumption of fish and seafood. Those who eat freshwater fish may be especially at risk since freshwater and its biota typically display higher PFOS concentrations than marine systems. In this study, we estimated the range in PFOS intake among average Swedish "normal" and "high" consumers of freshwater fish. By average we mean persons of average weight who eat average-sized portions. The "normal consumers" were assumed to eat freshwater fish 3 times per year, and the "high consumers" once a week. Under these assumptions, the yearly tolerable intake for "normal" and "high" consumers is reached when the PFOS concentrations in fish equals 59 and 3.4 mu g per kg fish meat. For this study, PFOS concentrations in the muscle tissue of edible-sized perch, pike and pikeperch were retrieved from three different Swedish datasets, covering both rural and urban regions and a total of 78 different inland waters. Mean PFOS concentrations in fish from these sites varied from 0.3 to 750 mu g/kg. From the available data, the annual min-max dietary PFOS intake for male "normal consumers" was found to be in the range 0.0021-5.4 mu g/kg/yr for the evaluated scenarios, with median values of 0.02-0.16 mu g/kg/yr. For male "high consumers", the total intake range was estimated to be 0.04-93 mu g/kg/yr, with median values being 0.27-1.6 mu g/kg/yr. For women, the exposure estimates were slightly lower, about 79% of the exposure in men. Despite highly variable PFOS concentrations in fish from different sites, we conclude that the three most commonly consumed freshwater species in Sweden constitute an important source for the total annual intake even for people who eat this kind of fish only a few times per year. The analyses of PFOA, PFNA and PFHxS showed values which were all below detection limit, and their contribution to the total PFAS intake via freshwater fish consumption is negligible in comparison to PFOS

Comparison of aromatic hydrocarbon measurements made by PTR-MS, DOAS and GC-FID during the MCMA 2003 Field Experiment

A comparison of aromatic hydrocarbon measurements is reported for the CENICA supersite in the district of Iztapalapa during the Mexico City Metropolitan Area field experiment in April 2003 (MCMA 2003). Data from three different measurement methods were compared: a Proton Transfer Reaction Mass Spectrometer (PTR-MS), long path measurements using a UV Differential Optical Absorption Spectrometer (DOAS), and Gas Chromatography-Flame Ionization analysis (GC-FID) of canister samples. The principle focus was on the comparison between PTR-MS and DOAS data. Lab tests established that the PTR-MS and DOAS calibrations were consistent for a suite of aromatic compounds including benzene, toluene, p-xylene, ethylbenzene, 1,2,4-trimethylbenzene, phenol and styrene. The point sampling measurements by the PTR-MS and GC-FID showed good correlations (r=0.6), and were in reasonable agreement for toluene, C2-alkylbenzenes and C3-alkylbenzenes. The PTR-MS benzene data were consistently high, indicating interference from ethylbenzene fragmentation for the 145 Td drift field intensity used in the experiment. Correlations between the open-path data measured at 16-m height over a 860-m path length (retroreflector in 430 m distance), and the point measurements collected at 37-m sampling height were best for benzene (r=0.61), and reasonably good for toluene, C2-alkylbenzenes, naphthalene, styrene, cresols and phenol (r>0.5). There was good agreement between DOAS and PTR-MS measurements of benzene after correction for the PTR-MS ethylbenzene interference. Mixing ratios measured by DOAS were on average a factor of 1.7 times greater than the PTR-MS data for toluene, C2-alkylbenzenes, naphthalene and styrene. The level of agreement for the toluene data displayed a modest dependence on wind direction, establishing that spatial gradients – horizontal, vertical, or both – in toluene mixing ratios were significant, and up to a factor of 2 despite the fact that all measurements were conducted above roof level. Our analysis highlights a potential problem in defining a VOC sampling strategy that is meaningful for the comparison with photochemical transport models: meaningful measurements require a spatial fetch that is comparable to the grid cell size of models, which is typically a few 10 km2. Long-path DOAS measurements inherently average over a larger spatial scale than point measurements. The spatial representativeness can be further increased if observations are conducted outside the surface roughness sublayer, which might require measurements at altitudes as high as 10 s of metres above roof level.Alexander von Humboldt-Stiftung (Feodor Lynen fellowship)Henry & Camille Dreyfus Foundation (Postdoctral Fellowship in Environmental Chemistry

Evaluation of a Consumer-Generated Marketing Plan for Medication Therapy Management Services

The purpose of this project was to utilize a consumer-directed, care model redesign methodology to develop and evaluate a marketing plan for medication therapy management services (MTMS) provided in community pharmacies. This was accomplished through a six-step process: (1) application of "design thinking" for eliciting consumer input on redesigning MTMS and marketing approaches, (2) exploratory research, (3) focus group analysis, (4) marketing plan development, (5) marketing plan implementation, and (6) marketing plan evaluation. The findings showed that the application of "design thinking" and focus group analysis was useful for creating a consumer-directed marketing plan for medication therapy management services (MTMS). Implementation and evaluation of the MTMS Marketing Plan revealed that the most successful pharmacies were those that had established business associate agreements with the medical clinics closest to their site of practice, including access to electronic health records. This "virtual electronic presence" of pharmacists in the medical care system was highly consistent with the consumer demand we uncovered for a visible relationship between pharmacists, physicians and other health care providers.   Type: Original Researc

Differential impact of glucose administered intravenously and orally on circulating mir-375 levels in human subjects

Background: To date, numerous nucleic acid species have been detected in the systemic circulation including microRNAs (miRNAs); however their functional role in this compartment remains unclear. Objective: The aim of this study was to determine whether systemic levels of miRNAs abundant in blood, including the neuroendocrine tissue-enriched miR-375, are altered in response to a glucose challenge. Design: Twelve healthy males were recruited for an acute cross-over study which consisted of two tests each following an eight-hour fasting period. An oral glucose tolerance test (OGTT) was performed and blood samples were collected over a 3-hour period. Following a period of at least one week, the same participants were administered an isoglycemic intravenous glucose infusion (IIGI) with the same blood collection protocol. Results: The glucose response curve following the IIGI mimicked that obtained after the OGTT, but as expected systemic insulin levels were lower during the IIGI compared to the OGTT (P<0.05). MiR-375 levels in circulation were increased only in response to an OGTT and not during an IIGI. In addition, the response to the OGTT also coincided with the transient increase of circulating glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), and glucose-dependent insulinotropic polypeptide (GIP). Conclusions: The present findings show levels of miR-375 increase following administration of an OGTT and in light of its enrichment in cells of the gut, suggest that the gastrointestinal tract may play a significant role to the abundance and function of this microRNA in the blood

Association between amygdala reactivity and a dopamine transporter gene polymorphism

Essential for detection of relevant external stimuli and for fear processing, the amygdala is under modulatory influence of dopamine (DA). The DA transporter (DAT) is of fundamental importance for the regulation of DA transmission by mediating reuptake inactivation of extracellular DA. This study examined if a common functional variable number tandem repeat polymorphism in the 3′ untranslated region of the DAT gene (SLC6A3) influences amygdala function during the processing of aversive emotional stimuli. Amygdala reactivity was examined by comparing regional cerebral blood flow, measured with positron emission tomography and [15O]water, during exposure to angry and neutral faces, respectively, in a Swedish sample comprising 32 patients with social anxiety disorder and 17 healthy volunteers. In a separate US sample, comprising 85 healthy volunteers studied with blood oxygen level-dependent functional magnetic resonance imaging, amygdala reactivity was assessed by comparing the activity during exposure to threatening faces and neutral geometric shapes, respectively. In both the Swedish and the US sample, 9-repeat carriers displayed higher amygdala reactivity than 10-repeat homozygotes. The results suggest that this polymorphism contributes to individual variability in amygdala reactivity

Distribution, magnitudes, reactivities, ratios and diurnal patterns of volatile organic compounds in the Valley of Mexico during the MCMA 2002 and 2003 field campaigns

International audienceA wide array of volatile organic compound (VOC) measurements was conducted in the Valley of Mexico during the MCMA-2002 and 2003 field campaigns. Study sites included locations in the urban core, in a heavily industrial area and at boundary sites in rural landscapes. In addition, a novel mobile-laboratory-based conditional sampling method was used to collect samples dominated by fresh on-road vehicle exhaust to identify those VOCs whose ambient concentrations were primarily due to vehicle emissions. Five distinct analytical techniques were used: whole air canister samples with Gas Chromatography/Flame Ionization Detection (GC-FID), on-line chemical ionization using a Proton Transfer Reaction Mass Spectrometer (PTR-MS), continuous real-time detection of olefins using a Fast Olefin Sensor (FOS), and long path measurements using UV Differential Optical Absorption Spectrometers (DOAS). The simultaneous use of these techniques provided a wide range of individual VOC measurements with different spatial and temporal scales. The VOC data were analyzed to understand concentration and spatial distributions, diurnal patterns, origin and reactivity in the atmosphere of Mexico City. The VOC burden (in ppbC) was dominated by alkanes (60%), followed by aromatics (15%) and olefins (5%). The remaining 20% was a mix of alkynes, halogenated hydrocarbons, oxygenated species (esters, ethers, etc.) and other unidentified VOCs. However, in terms of ozone production, olefins were the most relevant hydrocarbons. Elevated levels of toxic hydrocarbons, such as 1,3-butadiene, benzene, toluene and xylenes were also observed. Results from these various analytical techniques showed that vehicle exhaust is the main source of VOCs in Mexico City and that diurnal patterns depend on vehicular traffic. Finally, examination of the VOC data in terms of lumped modeling VOC classes and its comparison to the VOC lumped emissions reported in other photochemical air quality modeling studies suggests that some, but not all, VOC classes are underestimated in the emissions inventory by factors of 1.1 to 3

Distribution, magnitudes, reactivities, ratios and diurnal patterns of volatile organic compounds in the Valley of Mexico during the MCMA 2002 & 2003 field campaigns

A wide array of volatile organic compound (VOC) measurements was conducted in the Valley of Mexico during the MCMA-2002 and 2003 field campaigns. Study sites included locations in the urban core, in a heavily industrial area and at boundary sites in rural landscapes. In addition, a novel mobile-laboratory-based conditional sampling method was used to collect samples dominated by fresh on-road vehicle exhaust to identify those VOCs whose ambient concentrations were primarily due to vehicle emissions. Four distinct analytical techniques were used: whole air canister samples with Gas Chromatography/Flame Ionization Detection (GC-FID), on-line chemical ionization using a Proton Transfer Reaction Mass Spectrometer (PTR-MS), continuous real-time detection of olefins using a Fast Olefin Sensor (FOS), and long path measurements using UV Differential Optical Absorption Spectrometers (DOAS). The simultaneous use of these techniques provided a wide range of individual VOC measurements with different spatial and temporal scales. The VOC data were analyzed to understand concentration and spatial distributions, diurnal patterns, origin and reactivity in the atmosphere of Mexico City. The VOC burden (in ppbC) was dominated by alkanes (60%), followed by aromatics (15%) and olefins (5%). The remaining 20% was a mix of alkynes, halogenated hydrocarbons, oxygenated species (esters, ethers, etc.) and other unidentified VOCs. However, in terms of ozone production, olefins were the most relevant hydrocarbons. Elevated levels of toxic hydrocarbons, such as 1,3-butadiene, benzene, toluene and xylenes, were also observed. Results from these various analytical techniques showed that vehicle exhaust is the main source of VOCs in Mexico City and that diurnal patterns depend on vehicular traffic in addition to meteorological processes. Finally, examination of the VOC data in terms of lumped modeling VOC classes and its comparison to the VOC lumped emissions reported in other photochemical air quality modeling studies suggests that some alkanes are underestimated in the emissions inventory, while some olefins and aromatics are overestimated

Politicizing food security governance through participation: opportunities and opposition

Since the 2007/08 food price crisis there has been a proliferation of multi-stakeholder processes (MSPs) devoted to bringing diverse perspectives together to inform and improve food security policy. While much of the literature highlights the positive contributions to be gained from an opening-up of traditionally state-led processes, there is a strong critique emerging to show that, in many instances, MSPs have de-politicizing effects. In this paper, we scrutinize MSPs in relation to de-politicization. We argue that re-building sustainable and just food systems requires alternative visions that can best be made visible through politicized policy processes. Focusing on three key conditions of politicization, we examine the UN Committee on World Food Security as a MSP where we see a process of politicization playing out through the endorsement of the ‘most-affected’ principle, which is in turn being actively contested by traditionally powerful actors. We conclude that there is a need to implement and reinforce mechanisms that deliberately politicize participation in MSPs, notably by clearly distinguishing between states and other stakeholders, as well as between categories of non-state actors.</p

Effects of two common polymorphisms in the 3' untranslated regions of estrogen receptor β on mRNA stability and translatability

Estrogen signaling is mediated by estrogen receptors (ERs), ERα and ERβ. Aberrant estrogen signaling is involved in breast cancer development. ERα is one of the key biomarkers for diagnosis and treatment of breast cancer. Unlike ERα, ERβ is still not introduced as a marker for diagnosis and established as a target of therapy. Numerous studies suggest antiproliferative effects of ERβ, however its role remains to be fully explored. Albeit important, ERα is not a perfect marker, and some aspects of ERα function are still unclear. This thesis aims to characterize distinct molecular facets of ER action relevant for breast cancer and provide valuable information for ER-based diagnosis and treatment design. In PAPER I, we analyzed the functionality of two common single nucleotide polymorphisms in the 3’ untranslated regions of ERβ, rs4986938 and rs928554, which have been extensively investigated for association with various diseases. A significant difference in allelic expression was observed for rs4986938 in breast tumor samples from heterozygous individuals. However, no difference in mRNA stability or translatability between the alleles was observed. In PAPER II, we provided a more comprehensive understanding of ERβ function independent of ERα. A global gene expression analysis in a HEK293/ERβ cell model identified a set of ERβ-regulated genes. Gene Ontology (GO) analysis showed that they are involved in cell-cell signaling, morphogenesis and cell proliferation. Moreover, ERβ expression resulted in a significant decrease in cell proliferation. In PAPER III, using the human breast cancer MCF-7/ERβ cell model, we demonstrated, for the first time, the binding of ERα/β heterodimers to various DNA-binding regions in intact chromatin. In PAPER IV, we investigated a potential cross-talk between estrogen signaling and DNA methylation by identifying their common target genes in MCF-7 cells. Gene expression profiling identified around 150 genes regulated by both 17β- estradiol (E2) and a hypomethylating agent 5-aza-2’-deoxycytidine. Based on GO analysis, CpG island prediction analysis and previously reported ER binding regions, we selected six genes for further analysis. We identified BTG3 and FHL2 as direct target genes of both pathways. However, our data did not support a direct molecular interplay of mediators of estrogen and epigenetic signaling at promoters of regulated genes. In PAPER V, we further explored the interactions between estrogen signaling and DNA methylation, with focus on DNA methyltransferases (DNMT1, DNMT3a and DNMT3b). E2, via ERα, up-regulated DNMT1 and down-regulated DNMT3a and DNMT3b mRNA expression. Furthermore, DNMT3b interacted with ERα. siRNA-mediated DNMT3b depletion increased the expression of two genes, CDKN1A and FHL2. We proposed that the molecular mechanism underlying regulation of FHL2 and CDKN1A gene expression involves interplay of DNMT3b and ERα. In conclusion, the studies presented in this thesis contribute to the knowledge of ERβ function, and give additional insight into the cross-talk mechanisms underlying ERα signaling with ERβ and with DNA methylation pathways