Role of the Placental Vitamin D Receptor in Modulating Feto-Placental Growth in Fetal Growth Restriction and Preeclampsia-Affected Pregnancies

Fetal growth restriction (FGR) is a common pregnancy complication that affects up to 5% of pregnancies worldwide. Recent studies demonstrate that Vitamin D deficiency is implicated in reduced fetal growth, which may be rescued by supplementation of Vitamin D. Despite this, the pathway(s) by which Vitamin D modulate fetal growth remains to be investigated. Our own studies demonstrate that the Vitamin D receptor (VDR) is significantly decreased in placentae from human pregnancies complicated by FGR and contributes to abnormal placental trophoblast apoptosis and differentiation and regulation of cell-cycle genes in vitro. Thus, Vitamin D signaling is important for normal placental function and fetal growth. This review discusses the association of Vitamin D with fetal growth, the function of Vitamin D and its receptor in pregnancy, as well as the functional significance of a placental source of Vitamin D in FGR. Additionally, we propose that for Vitamin D to be clinically effective to prevent and manage FGR, the molecular mechanisms of Vitamin D and its receptor in modulating fetal growth requires further investigation

Elliptic Flow in Au+Au Collisions at RHIC

Elliptic flow is an interesting probe of the dynamical evolution of the dense system formed in the ultrarelativistic heavy ion collisions at the Relativistic Heavy Ion Collider (RHIC). The elliptic flow dependences on transverse momentum, centrality, and pseudorapidity were measured using data collected by the PHOBOS detector, which offers a unique opportunity to study the azimuthal anisotropies of charged particles over a wide range of pseudorapidity. These measurements are presented, together with an overview of the analysis methods and a discussion of the results.Comment: Presented at Hot Quarks 2004; 7 pages, 6 figure

Nano-Architecture of nitrogen-doped graphene films synthesized from a solid CN source

New synthesis routes to tailor graphene properties by controlling the concentration and chemical configuration of dopants show great promise. Herein we report the direct reproducible synthesis of 2-3% nitrogen-doped ‘few-layer’ graphene from a solid state nitrogen carbide a-C:N source synthesized by femtosecond pulsed laser ablation. Analytical investigations, including synchrotron facilities, made it possible to identify the configuration and chemistry of the nitrogen-doped graphene films. Auger mapping successfully quantified the 2D distribution of the number of graphene layers over the surface, and hence offers a new original way to probe the architecture of graphene sheets. The films mainly consist in a Bernal ABA stacking three-layer architecture, with a layer number distribution ranging from 2 to 6. Nitrogen doping affects the charge carrier distribution but has no significant effects on the number of lattice defects or disorders, compared to undoped graphene synthetized in similar conditions. Pyridinic, quaternary and pyrrolic nitrogen are the dominant chemical configurations, pyridinic N being preponderant at the scale of the film architecture. This work opens highly promising perspectives for the development of self-organized nitrogen-doped graphene materials, as synthetized from solid carbon nitride, with various functionalities, and for the characterization of 2D materials using a significant new methodology

Combinatorial polymeric conjugated micelles with dual cytotoxic and antiangiogenic effects for the treatment of ovarian cancer

Emerging treatment paradigms like targeting the tumor microenvironment and/or dosing as part of a metronomic regimen are anticipated to produce better outcomes in ovarian cancer, but current drug delivery systems are lacking. We have designed and evaluated paclitaxel (PTX) and rapamycin (RAP) micellar systems that can be tailored for various dosing regimens and target tumor microenvironment. Individual and mixed PTX/RAP (MIX-M) micelles are prepared by conjugating drugs to a poly­(ethylene glycol)-<i>block</i>-poly­(β-benzyl l-aspartate) using a pH-sensitive linker. The micelles release the drug(s) at pH 5.5 indicating preferential release in the acidic endosomal/lysosomal environment. Micelles exhibit antiproliferative effects in ovarian cell cancer lines (SKOV-3 (human caucasian ovarian adenocarcinoma) and ES2 (human ovarian clear cell carcinoma)) and an endothelial cell line (HUVEC; human umbilical vein endothelial cells) with the MIX-M being synergistic. The micelles also inhibited endothelial migration and tube formation. In healthy mice, micelles at 60 mg/kg/drug demonstrated no acute toxicity over 21 days. ES2 xenograft model efficacy studies at 20 mg/kg/drug dosed every 4 days and evaluated at 21 days indicate that the individual micelles exhibit antiangiogenic effects, while the MIX-M exhibited both antiangiogenic and apoptotic induction that results in significant tumor volume reduction. On the basis of our results, MIX-M micelles can be utilized to achieve synergistic apoptotic and antiangiogenic effects when treated at frequent low doses

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

Dendritic cells from aged subjects contribute to chronic airway inflammation by activating bronchial epithelial cells under steady state

The mechanisms underlying the increased susceptibility of the elderly to respiratory infections are not well understood. The crosstalk between the dendritic cells (DCs) and epithelial cells is essential in maintaining tolerance as well as in generating immunity in the respiratory mucosa. DCs from aged subjects display an enhanced basal level of activation, which can affect the function of epithelial cells. Our results suggest that this is indeed the scenario as exposure of primary bronchial epithelial cells (PBECs) to supernatants from unstimulated DCs of aged subjects resulted in activation of PBECs. The expression of CCL20, CCL26, CXCL10, mucin, and CD54 was significantly increased in the PBECs exposed to aged DC supernatants, but not to young DC supernatants. Furthermore, aged DC supernatants also enhanced the permeability of the PBEC barrier. We also found that DCs from aged subjects spontaneously secreted increased levels of pro-inflammatory mediators, interleukin-6, tumor necrosis factor (TNF)-α, and metalloproteinase A disintegrin family of metalloproteinase 10, which can affect the functions of PBECs. Finally, we demonstrated that TNF-α, present in the supernatant of DCs from aged subjects, was the primary pro-inflammatory mediator that affected PBEC functions. Thus, age-associated alterations in DC–epithelial interactions contribute to chronic airway inflammation in the elderly, increasing their susceptibility to respiratory diseases

A global experiment on motivating social distancing during the COVID-19 pandemic

Significance Communicating in ways that motivate engagement in social distancing remains a critical global public health priority during the COVID-19 pandemic. This study tested motivational qualities of messages about social distancing (those that promoted choice and agency vs. those that were forceful and shaming) in 25,718 people in 89 countries. The autonomy-supportive message decreased feelings of defying social distancing recommendations relative to the controlling message, and the controlling message increased controlled motivation, a less effective form of motivation, relative to no message. Message type did not impact intentions to socially distance, but people’s existing motivations were related to intentions. Findings were generalizable across a geographically diverse sample and may inform public health communication strategies in this and future global health emergencies. Abstract Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

Validation of super-emitter analysis

Met de landelijke aanpak piekbelasting wil het kabinet stikstofdepositie in kwetsbare natuurgebieden terugdringen. Onder de aanpak piekbelasting vallen verschillende regelingen, waaronder de ‘landelijke regeling om veehouderijen met piekbelasting te beëindigen’ (Lbv-plus). Voor de Lbv-plus liet het ministerie van Landbouw, Natuur en Voedselkwaliteit (LNV(Ministerie van Landbouw, Natuur en Voedselkwaliteit)) eerder vijf varianten doorrekenen om te bepalen onder welke voorwaarden bedrijven voor de regeling in aanmerking kunnen komen. Gekozen is voor de variant met bedrijven die de hoogste vracht aan stikstofdepositie veroorzaken op de overbelaste stikstofgevoelige Natura 2000-gebieden, binnen een straal van 25 kilometer rond het bedrijf. Er wordt dan ingegrepen op zo min mogelijk bedrijven om de grootste daling in de stikstofdepositie te bereiken. Op verzoek van LNV heeft het RIVM nu deze vijf varianten gecontroleerd. Het RIVM heeft dit met eigen berekeningen gedaan en hiervoor actuelere gegevens gebruikt. Hieruit blijkt dat de gekozen variant inderdaad de grootste stikstofwinst geeft. LNV verwacht dat 20 procent van de bedrijven die voor de aanpak piekbelasting in aanmerking komen, meedoen met de Lbv-plus. Dit zijn ongeveer 600 bedrijven. Als dat gebeurt, dan daalt de gemiddelde stikstofdepositie in de kwetsbare natuur naar schatting met ongeveer 40 mol stikstof per hectare per jaar, op een gemiddelde overbelasting van de kritische depositiewaarde (KDW) van 385 mol stikstof per hectare per jaar. Het werkelijke effect kan pas berekend worden als bekend is welke bedrijven er meedoen. Hun emissie en ligging ten opzichte van de natuur zijn hierbij bepalend en geven een marge van tientallen procenten op het resultaat. Daarnaast is natuurlijk het aantal deelnemers bepalend. LNV gaat uit van 600 bedrijven maar een range van 100 tot 700 bedrijven levert een depositiereductie van 7 tot 47 mol stikstof per hectare per jaar. Met de door het RIVM gebruikte actuelere gegevens daalde de geschatte depositie iets meer dan LNV eerder had laten berekenen. Dit heeft verschillende oorzaken. Het RIVM gebruikte bijvoorbeeld de emissiefactoren uit de Emissieregistratie om de depositie te bepalen, terwijl LNV eerder emissiefactoren uit de wettelijke ‘Rav-richtlijn’ gebruikte. Emissiefactoren uit de dagelijkse praktijk zijn hoger dan die in de Ravrichtlijn. Ook was in de nieuwere cijfers het aantal dieren hoger omdat het aantal dieren per bedrijf gemiddeld toeneemt.The government has adopted a national action plan to combat peak loads for the purpose of reducing nitrogen deposition in vulnerable nature conservation areas. The national action plan to combat peak loads comprises a number of schemes, including a national scheme (Lbv-plus) to close down livestock farms classified as nitrogen ‘superemitters’. Previously, the Ministry of Agriculture, Nature & Food Quality (LNV) commissioned an analysis to determine the conditions that businesses must meet in order to qualify for the Lbv-plus scheme. This yielded five possible variants. The government has opted for the variant that involves closing down the businesses that deposit the most nitrogen on overburdened and delicate Natura 2000 areas within a 25-kilometre radius. This variant strikes a balance between affecting the fewest possible businesses and achieving the greatest possible nitrogen deposition reduction. At LNV’s request, RIVM has now validated all five variants. To this end, RIVM performed its own calculations using more up-to-date data. Its conclusion is that the chosen variant is indeed the most efficient. LNV expects that 20 per cent of the businesses that qualify for the national action plan to combat peak loads will take part. This amounts to around 600 businesses. In this scenario, the average nitrogen deposition in vulnerable nature is estimated to fall by around 40 mol nitrogen per hectare per year, related to an average access of the critical level of 269 mol nitrogen per hectare per year. The actual effect will be calculated when it is known which businesses will take part. Using the more up-to-date data, the estimated nitrogen deposition reduction is slightly greater than the figure LNV had previously calculated. There are several possible reasons for this. For instance, RIVM used the emission factors from the Netherlands’ Emissions Registration, while the earlier analysis commissioned by LNV used the emission factors from the statutory Ammonia and Livestock Farming Guideline (Richtlijn Ammoniak en Veehouderij, RAV). Emission factors from everyday practice are slightly higher than those from the RAV. Moreover, the latest data assumed a greater number of animals, given the average rise in the number of animals per livestock farm. Participation in the national action plan to combat peak loads is voluntary. Around 3,000 super-emitters, i.e., the businesses that deposit the most nitrogen in Natura 2000 areas, qualify to take part. These are mainly livestock farms and several industrial businesses. They have various options at their disposal to reduce nitrogen deposition, such as keeping fewer animals, innovating, relocating, or closing down

The Effect of Contact Lens Induced Corneal Edema on Goldmann Applanation Tonometry Measurements

Aim: To determine the effect of small increases in corneal hydration on the accuracy of Goldmann applanation tonometry estimates of intraocular pressure (IOP). Materials and Methods: Twenty-five young healthy subjects presented on 3 separate days approximately 1 week apart. On 2 visits, subjects were required to wear a hydrogel contact lens with either a center thickness of 0.3 and 0.7 mm (HEMA 38% water content, parallel surface curve) in 1 eye only under closed-eye conditions for 2 hours to induce corneal swelling. The third visit acted as a control. IOP, corneal thickness, and corneal curvature were measured in both eyes before and after contact lens wear on all visits. Results: There was a statistically significant increase in corneal thickness of 40.2±14.4 μm (P<0.001) and 41.9±16.4 μm (P<0.001) after wearing the 0.3 and 0.7 mm thick contact lenses, respectively (2-tailed paired t test). There was an increase in IOP of 2.8±2.2 mm Hg (P<0.001) after wearing the 0.3 mm thick contact lens, and a statistically insignificant difference of 1.3±3.0 mm Hg (P=0.058) after wearing the 0.7 mm thick contact lens (2-tailed paired t test). There was a statistically significant Pearson correlation between the change in corneal thickness and the change in IOP after lens wear (r=0.500, P<0.001, 0.3 mm lens and r=0.399, P<0.001, 0.7 mm lens). The corneal hydration-induced measurement error was 0.46 mm Hg per 10 μm change in corneal thickness (0.3 mm lens) and 0.35 mm Hg per 10 μm change in corneal thickness (0.7 mm lens). Conclusion: A small increase in corneal hydration and thickness may cause a clinically significant overestimation of IOP when measured using Goldmann applanation tonometry