Does the use of a vascular contrast agent facilitate earlier detection of maternal flow to the placental intervillous space (IVS) in the first trimester of pregnancy?
Microvascular filling of the IVS ...was demonstrated by contrast-enhanced ultrasound from 6 weeks of gestation onwards, earlier than previously believed.
During placental establishment and remodeling of maternal spiral arteries, endovascular trophoblast cells invade and accumulate in the lumen of these vessels to form 'trophoblast plugs'. Prior evidence from morphological and Doppler ultrasound studies has been conflicting as to whether the spiral arteries are completely plugged, preventing maternal blood flow to the IVS until late in the first trimester.
Uteroplacental flow was examined across the first trimester in human subjects given an intravenous infusion of lipid-shelled octofluoropropane microbubbles with ultrasound measurement of destruction and replenishment kinetics. We also performed a comprehensive histopathological correlation using two separately archived uteroplacental tissue collections to evaluate the degree of spiral artery plugging and evaluate remodeling of the upstream myometrial radial and arcurate arteries.
Pregnant women (n = 34) were recruited in the first trimester (range: 6+3 to 13+6 weeks gestation) for contrast-enhanced ultrasound studies with destruction-replenishment analysis of signal intensity for assessment of microvascular flux rate. Histological samples from archived in situ (Boyd Collection, n = 11) and fresh first, second, and third trimester decidual and post-hysterectomy uterine specimens (n = 16) were evaluated by immunohistochemistry (using markers of epithelial, endothelial and T-cells, as well as cell adhesion and proliferation) and ultrastructural analysis.
Contrast agent entry into the IVS was visualized as early as 6+3 weeks of gestation with some variability in microvascular flux rate noted in the 6-7+6 week samples. Spiral artery plug canalization was observed from 7 weeks with progressive disintegration thereafter. Of note, microvascular flux rate did not progressively increase until 13 weeks, which suggests that resistance to maternal flow in the early placenta may be mediated more proximally by myometrial radial arteries that begin remodeling at the end of the first trimester.
Gestational age was determined by crown-rump length measurements obtained by transvaginal ultrasound on the day of contrast-enhanced imaging studies, which may explain the variability in the earliest gestational age samples due to the margin of error in this type of measurement.
Our comprehensive in situ histological analysis, in combination with the use of an in vivo imaging modality that has the sensitivity to permit visualization of microvascular filling, has allowed us to reveal new evidence in support of increasing blood flow to the IVS from 6 weeks of gestation. Histologic review suggested the mechanism may be blood flow through capillary-sized channels that form through the loosely cohesive 'plugs' by 7 weeks gestation. However, spiral artery remodeling on its own did not appear to explain why there is significantly more blood flow at 13 weeks gestation. Histologic studies suggest it may be related to radial artery remodeling, which begins at the end of the first trimester.
This project was supported by the Oregon Health and Science University Knight Cardiovascular Institute, Center for Developmental Health and the Struble Foundation. There are no competing interests.
The microstructure of QMG consists of a single crystal REBa2Cu3Ox phase and fine RE2BaCuO5 particles. Y-based QMG was first produced in 1988 by the Quench and Melt Growth method. A bulk magnet made ...from QMG was proposed in 1989. QMG bulk magnets were realized by enlargement technology using RE substitute seed crystals. Based on these technological innovations, the development of NMR and MDDS, which are product-based applications of bulk magnets, has recently been reported from the research institutes of applied development. The history of the initial development of these QMG materials and QMG bulk magnets was reviewed. In addition, as progress of the recent QMG bulk magnet development, a new reinforcement method for large ring bulk magnets that can trap 10 T class strong magnetic field magnetization has been reported. For high field magnetization, the reinforcement of bulk magnets is essential to prevent cracking due to large hoop force. Compared to the conventional reinforcement method using only the outer metal ring, the new reinforcement method has been developed using thin QMG rings and metal ring sheets as the composite material with the inner and outer metal rings. In the case of the QMG ring reinforced by the conventional method, cracking occurred at 10T magnetization. Whereas the QMG ring created by the new reinforcement method successfully trapped approximately 10 T.
Tyler (Journal of Physiology 228 (1973) 637–647) reported that the sensitivity function for curvature detection has band-pass characteristics with respect to shape frequency. The shape of this ...function suggests that the curvature detection mechanism might consist of a set of sub-mechanisms each tuned for shape frequencies similar to mechanisms for contrast detection. In Experiment 1, we applied an adaptation for shape frequency to investigate whether shape frequency is the critical feature in curvature detection. We successfully replicated the U shape threshold function reported by Tyler (1973), but found that selective adaptation does not occur for shape frequency. These results suggest that shape frequency is not critical for curvature detection. In Experiment 2, we examined the possibility that curvature detection for the highest sensitivity range is mediated by a displacement process similar to that for Vernier acuity. The results indicate that curvature detection for this range is mediated by a mechanism that is sensitive to spatial displacement, and suggests the existence of a common mechanism for spatial displacement that mediates both curvature and Vernier detections. By comparing our results with those of several previous studies, we concluded that the apparent band-pass characteristic for curvature detection is produced by combining the characteristics of three separate limiting factors: local orientation at lower frequencies, spatial acuity at higher frequencies, and displacement in the highest sensitivity area.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Global climate change is expected to affect future rainfall patterns. These changes should be taken into account when assessing future flooding risks. This study presents a method for quantifying the ...increase in flood risk caused by global climate change for use in urban flood risk management. Flood risk in this context is defined as the product of flood damage potential and the probability of its occurrence. The study uses a geographic information system-based flood damage prediction model to calculate the flood damage caused by design storms with different return periods. Estimation of the monetary damages these storms produce and their return periods are precursors to flood risk calculations. The design storms are developed from modified intensity-duration-frequency relationships generated by simulations of global climate change scenarios (e.g. CGCM2A2). The risk assessment method is applied to the Kanda River basin in Tokyo, Japan. The assessment provides insights not only into the flood risk cost increase due to global warming, and the impact that increase may have on flood control infrastructure planning.
This paper describes the progress in quench melt-growth (QMG) bulk magnets, developed by the Nippon Steel & Sumitomo Metal Corporation, which consist of single crystalline RE123 phase and finely ...dispersed RE211 particles. QMG bulks can trap high magnetic fields. The field-trapping ability of QMG bulks is largely increased with an improvement in its Jc and size, promising the realization of various applications such as flywheel energy-storage systems, ship motors, NMR/MRI spectrometers, wind-power generators and so on. Intensive research has revealed that the optimal RE element is different depending on application requirements. Gd-QMG bulk is the most promising material for several high-field engineering applications. The trapped magnetic field of Gd-QMG bulk 60 mm in diameter at 77 K is twice as large as that of Y-QMG bulk with a similar size due to its excellent Jc properties. The large Gd-based QMG bulks up to 150 mm in diameter are fabricated by incorporating the RE compositional gradient method. Compact NMR/MRI spectrometers are one of the promising applications of bulk superconductors. Eu-QMG bulks are suitable for NMR magnets. NMR applications require extremely homogeneous magnetic fields. In the Eu-system, the small paramagnetic moment of a Eu ion compared to a Gd ion improves the field homogeneity in the bulk. For the application of current leads, Dy-based QMG is available by utilizing a low thermal conductivity.
The problem of uneven distribution of medical services and inequitable distribution of physicians is drawing much attention worldwide. Revealing how changes in the specialty training system in Japan ...have affected the distribution of doctors could help us understand this problem. In 2018, a new and standardized specialty training system was implemented by the Japanese Medical Specialty Board, which is recognized by the Ministry of Health, Labor and Welfare. The purpose of this study was to investigate how this new system has affected the geographical distribution of doctors commencing specialty training (trainees) and choice of specialty in Japan.
Retrospective observational study.
The change in the number of trainees between the control period (2012–2014) and 2018 was investigated, taking into account the prefecture and specialty selected. Population, the proportion of residents aged 65 years or older (aging rate), and the total number of overall doctors in each prefecture were considered as the background characteristics of each prefecture. We created a Lorenz curve and calculated the Gini coefficient for the distribution of trainees.
In 2018, the number of trainees per 100,000 population increased to 6.6 nationwide compared with 5.5 during the control period. The number of trainees per 100,000 population in 2018 increased in prefectures with a large population of ≧ 2,000,000, a low aging rate (<27%), and a high doctor density (≧ 250 doctors per 100,000 population). The Gini coefficient showed an increase to 0.226 in 2018 compared with only 0.160 during the control period.
After the implementation of the new training system, there was an increase in the number of doctors enrolling in specialty programs, and the specialties other than internal medicine and surgery have attracted more trainees. Inequality in the distribution of doctors between urban and rural prefectures worsened. This indicates the need to explore new ways of balancing distribution while maintaining optimal opportunities for specialist training.
•In 2018, the Japanese Medical Specialty Board implemented a new and standardized physician specialty training system in Japan.•We investigated the change in the number of trainees between the control period (2012–2014) and 2018.•The total number of trainees and that per 100,000 population showed an increase in all specialties.•The Gini coefficient showed an increase to 0.226 in 2018 compared with only 0.160 during the control period.•Seeking ways of balancing trainees's unevenness while maintaining optimal opportunities for specialist training is needed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The use of environmental tracers brings comprehensive benefits to the management of water resources since it helps to prevent their pollution, minimize public health risks, and thus reduce the impact ...of urbanization. In Brazil, the Guarani Aquifer System (GAS) has strategic and environmental importance, making its preservation and sustainable exploitation mandatory. The present study aimed at evaluating sources of contamination in the GAS using the combination of geochemical data and two environmental tracers: nitrate isotopes (
15
N
NO3
and
18
O
NO3
) and one rare earth element (Gadolinium—Gd). For that, five wells—four exploiting the GAS and one the Bauru Aquifer System (BAS)—were selected to discuss the human inputs in groundwater used for public supply in an urban area. Traditional physicochemical analyses were conducted for six campaign samplings and nitrate monitoring for this period was evaluated on a time scale, also considering the accumulated rainfall. Besides that, the double isotopic method (DIM), e.g., δ
18
O
NO3
e δ
15
N
NO3
, was applied to identify the fractionation and enable the distinction of the nitrate contamination source. In addition, the determination of anomalies of Gd, a wastewater-derived contaminant, was also performed to verify recent human inputs in groundwater. The results show that the local existence of nitrate in the GAS and BAS—even at low concentrations (values from 0.26 to 6.68 mg L
−1
)—originated from anthropogenic inputs (septic waste), as indicates the typical isotopic signals ratio in the isotopic approach. Associated with that, the evaluation of Gd permitted the separation of groundwater samples into older or more recent leakages. The use of environmental tracers to assess anthropogenic inputs in groundwater reiterates the importance of adopting more effective protection strategies for water resources management systems, in order to prevent contamination.
Graphical Abstract
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Although vital pulp therapy should be performed by promoting the wound-healing capacity of dental pulp, existing pulp-capping materials were not developed with a focus on the pulpal repair process. ...In previous investigations of wound healing in dental pulp, we found that organic dentin matrix components (DMCs) were degraded by matrix metalloproteinase-20, and DMC degradation products containing protein S100A7 (S100A7) and protein S100A8 (S100A8) promoted the pulpal wound-healing process. However, the direct use of recombinant proteins as pulp-capping materials may cause clinical problems or lead to high medical costs. Thus, we hypothesized that functional peptides derived from recombinant proteins could solve the problems associated with direct use of such proteins. In this study, we identified functional peptides derived from the protein S100 family and investigated their effects on dental pulp tissue. We first performed amino acid sequence alignments of protein S100 family members from several mammalian sources, then identified candidate peptides. Next, we used a peptide array method that involved human dental pulp stem cells (hDPSCs) to evaluate the mineralization-inducing ability of each peptide. Our results supported the selection of 4 candidate functional peptides derived from proteins S100A8 and S100A9. Direct pulp-capping experiments in a rat model demonstrated that 1 S100A8-derived peptide induced greater tertiary dentin formation compared with the other peptides. To investigate the mechanism underlying this induction effect, we performed liquid chromatography–tandem mass spectrometry analysis using hDPSCs and the S100A8-derived peptide; the results suggested that this peptide promotes tertiary dentin formation by inhibiting inflammatory responses. In addition, this peptide was located in a hairpin region on the surface of S100A8 and could function by direct interaction with other molecules. In summary, this study demonstrated that a S100A8-derived functional peptide promoted wound healing in dental pulp; our findings provide insights for the development of next-generation biological vital pulp therapies.
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CMK, NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
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