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Background/Aims: Gestational diabetes (GDM) might be associated with alterations in the metabolomic profile of affected mothers and their offspring. Until now, there is a paucity of studies that investigated both, the maternal and the fetal serum metabolome in the setting of GDM. Mounting evidence suggests that the fetus is not just passively affected by gestational disease but might play an active role in it. Metabolomic studies performed in maternal blood and fetal cord blood could help to better discern distinct fetal from maternal disease interactions. Methods: At the time of birth, serum samples from mothers and newborns (cord blood samples) were collected and screened for 163 metabolites utilizing tandem mass spectrometry. The cohort consisted of 412 mother/child pairs, including 31 cases of maternal GDM. Results: An initial non-adjusted analysis showed that eight metabolites in the maternal blood and 54 metabolites in the cord blood were associated with GDM. After Benjamini-Hochberg (BH) procedure and adjustment for confounding factors for GDM, fetal phosphatidylcholine acyl-alkyl C 32:1 and proline still showed an independent association with GDM. Conclusions: This study found metabolites in cord blood which were associated with GDM, even after adjustment for established risk factors of GDM. To the best of our knowledge, this is the first study demonstrating an independent association between fetal serum metabolites and maternal GDM. Our findings might suggest a potential effect of the fetal metabolome on maternal GDM. (c) 2018 The Author(s) Published by S. Karger AG, Basel
Background/Aims: Impaired birth outcomes, like low birth weight, have consistently been associated with increased disease susceptibility to hypertension in later life. Alterations in the maternal or fetal metabolism might impact on fetal growth and influence birth outcomes. Discerning associations between the maternal and fetal metabolome and surrogate parameters of fetal growth could give new insight into the complex relationship between intrauterine conditions, birth outcomes, and later life disease susceptibility. Methods: Using flow injection tandem mass spectrometry, targeted metabolomics was performed in serum samples obtained from 226 mother/child pairs at delivery. Associations between neonatal birth weight and concentrations of 163 maternal and fetal metabolites were analyzed. Results: After FDR adjustment using the Benjamini-Hochberg procedure lysophosphatidylcholines (LPC) 14:0, 16:1, and 18:1 were strongly positively correlated with birth weight. In a stepwise linear regression model corrected for established confounding factors of birth weight, LPC 16: 1 showed the strongest independent association with birth weight (CI: 93.63 - 168.94; P = 6.94x10(-11)). The association with birth weight was stronger than classical confounding factors such as offspring sex (CI: - 258.81- -61.32; P = 0.002) and maternal smoking during pregnancy (CI: -298.74 - -29.51; P = 0.017). Conclusions: After correction for multiple testing and adjustment for potential confounders, LPC 16:1 showed a very strong and independent association with birth weight. The underlying molecular mechanisms linking fetal LPCs with birth weight need to be addressed in future studies. (c) 2018 The Author(s) Published by S. Karger AG, Basel
Scenarios have become a key tool for supporting sustainability research on regional and global change. In this study we evaluate four regional scenario assessments: first, to explore a number of research challenges related to sustainability science and, second, to contribute to sustainability research in the specific case studies. The four case studies used commonly applied scenario approaches that are (i) a story and simulation approach with stakeholder participation in the Oum Zessar watershed, Tunisia, (ii) a participatory scenario exploration in the Rwenzori region, Uganda, (iii) a model-based prepolicy study in the Inner Niger Delta, Mali, and (iv) a model coupling-based scenario analysis in upper Thukela basin, South Africa. The scenario assessments are evaluated against a set of known challenges in sustainability science, with each challenge represented by two indicators, complemented by a survey carried out on the perception of the scenario assessments within the case study regions. The results show that all types of scenario assessments address many sustainability challenges, but that the more complex ones based on story and simulation and model coupling are the most comprehensive. The study highlights the need to investigate abrupt system changes as well as governmental and political factors as important sources of uncertainty. For an in-depth analysis of these issues, the use of qualitative approaches and an active engagement of local stakeholders are suggested. Studying ecological thresholds for the regional scale is recommended to support research on regional sustainability. The evaluation of the scenario processes and outcomes by local researchers indicates the most transparent scenario assessments as the most useful. Focused, straightforward, yet iterative scenario assessments can be very relevant by contributing information to selected sustainability problems.
Para inicios del siglo XXI se instalan nuevos medios de crítica literaria a través de soportes digitales. Estas publicaciones tensionan un campo letrado chileno que enfrenta cuestionamientos. Gestionadas mayoritariamente por creadores precedentes de la generación del 90, producen reaproximaciones a la cultura letrada. El objetivo es desafiar dinámicas de interacción lectora heredadas vinculadas a las luces patria, desarrollistas, de tipo linear y ciegas a la heterogeneidad cultural vivida en la época. El proceso comprende, de tal modo, una reeducación crítica centrada en ensayar poéticas de productividad analítico-literarias heteróclitas. Se trata de una interacción lectora diversa, sujeta a retóricas íntimas de apreciación estética, que ponen en cuestión las nociones tradicionales mayoritariamente instructiva de la cultura chilena.
Background/Aims: Angiogenesis plays a key role during embryonic development. The vascular endothelin (ET) system is involved in the regulation of angiogenesis. Lipopolysaccharides (LPS) could induce angiogenesis. The effects of ET blockers on baseline and LPS-stimulated angiogenesis during embryonic development remain unknown so far. Methods: The blood vessel density (BVD) of chorioallantoic membranes (CAMs), which were treated with saline (control), LPS, and/or BQ123 and the ETB blocker BQ788, were quantified and analyzed using an IPP 6.0 image analysis program. Moreover, the expressions of ET-1, ET-2, ET3, ET receptor A (ETRA), ET receptor B (ETRB) and VEGFR2 mRNA during embryogenesis were analyzed by semi-quantitative RT-PCR. Results: All components of the ET system are detectable during chicken embryogenesis. LPS increased angiogenesis substantially. This process was completely blocked by the treatment of a combination of the ETA receptor blockers-BQ123 and the ETB receptor blocker BQ788. This effect was accompanied by a decrease in ETRA, ETRB, and VEGFR2 gene expression. However, the baseline angiogenesis was not affected by combined ETA/ETB receptor blockade. Conclusion: During chicken embryogenesis, the LPS-stimulated angiogenesis, but not baseline angiogenesis, is sensitive to combined ETA/ETB receptor blockade.
Breaking the Barrier
(2018)
Topical administration permits targeted, sustained delivery of therapeutics to human skin. Delivery to the skin, however, is typically limited to lipophilic molecules with molecular weight of < 500 Da, capable of crossing the stratum corneum. Nevertheless, there are indications protein delivery may be possible in barrier deficient skin, a condition found in several inflammatory skin diseases such as psoriasis, using novel nanocarrier systems. Methods: Water in water thermo-nanoprecipitation; dynamic light scattering; zeta potential measurement; nanoparticle tracking analysis; atomic force microscopy; cryogenic transmission electron microscopy; UV absorption; centrifugal separation membranes; bicinchoninic acid assay; circular dichroism; TNF alpha binding ELISA; inflammatory skin equivalent construction; human skin biopsies; immunohistochemistry; fluorescence microscopy; western blot; monocyte derived Langerhans cells; ELISA Results: Here, we report the novel synthesis of thermoresponsive nanogels (tNG) and the stable encapsulation of the anti-TNFa fusion protein etanercept (ETR) (similar to 150 kDa) without alteration to its structure, as well as temperature triggered release from the tNGs. Novel tNG synthesis without the use of organic solvents was conducted, permitting in situ encapsulation of protein during assembly, something that holds great promise for easy manufacture and storage. Topical application of ETR loaded tNGs to inflammatory skin equivalents or tape striped human skin resulted in efficient ETR delivery throughout the SC and into the viable epidermis that correlated with clear anti-inflammatory effects. Notably, effective ETR delivery depended on temperature triggered release following topical application. Conclusion: Together these results indicate tNGs hold promise as a biocompatible and easy to manufacture vehicle for stable protein encapsulation and topical delivery into barrier-deficient skin.
Earth’s surface temperature will continue to rise for another 20 to 30 years even with the strongest carbon emission reduction currently considered. The associated changes in rainfall patterns can result in an increased flood risk worldwide. We compute the required increase in flood protection to keep high-end fluvial flood risk at present levels. The analysis is carried out worldwide for subnational administrative units. Most of the United States, Central Europe, and Northeast and West Africa, as well as large parts of India and Indonesia, require the strongest adaptation effort. More than half of the United States needs to at least double their protection within the next two decades. Thus, the need for adaptation to increased river flood is a global problem affecting industrialized regions as much as developing countries.
This publication demonstrates the abilities of a precise and straightforward microcontact printing approach for the preparation of patchy silica particles. In a broad particle size range, it is possible to finely tune the number and parameters of three-dimensional patches like diameter and thickness using only polyethyleneimine ink, poly(dimethoxysilane) as stamp material and a suitable release solvent.
This study aimed to determine the specific physical and basic gymnastics skills considered critical in gymnastics talent identification and selection as well as in promoting men's artistic gymnastics performances. Fifty-one boys from a provincial gymnastics team (age 11.03 ± 0.95 years; height 1.33 ± 0.05 m; body mass 30.01 ± 5.53 kg; body mass index [BMI] 16.89 ± 3.93 kg/m²) regularly competing at national level voluntarily participated in this study. Anthropometric measures as well as the men's artistic gymnastics physical test battery (i.e., International Gymnastics Federation [FIG] age group development programme) were used to assess the somatic and physical fitness profile of participants, respectively. The physical characteristics assessed were: muscle strength, flexibility, speed, endurance, and muscle power. Test outcomes were subjected to a principal components analysis to identify the most representative factors. The main findings revealed that power speed, isometric and explosive strength, strength endurance, and dynamic and static flexibility are the most determinant physical fitness aspects of the talent selection process in young male artistic gymnasts. These findings are of utmost importance for talent identification, selection, and development.