The Circadian Rhythm of Blood Pressure During Pregnancy

To review the literature on the circadian rhythm of blood pressure during pregnancy. Data Sources : Computerized searches on MEDLINE, CINAHL, and MIRLYN. Study Selection : Selected studies from 1969 to 1997 were evaluated. Data Extraction : Data were extracted and information was organized under the following areas: definition of and the interconnection between circadian rhythm and blood pressure; the circadian variability of blood pressure throughout the trimesters; the patterns of the circadian rhythm of blood pressure in pregnancies defined as normal and those complicated by chronic hypertension and preeclampsia; and clinical implications. Data Synthesis : The circadian rhythm of blood pressure in pregnancy is the same as in the nonpregnant state, with a nocturnal decrease, especially during sleep. In patients with chronic hypertension, the nocturnal fall in blood pressure may be steeper. Patients with mild preeclampsia may experience a less pronounced nocturnal decrease in blood pressure. Patients with severe preeclampsia may display a reversed circadian rhythm, with no decrease and/or an increase in nocturnal blood pressure. Conclusions : The patterns of the circadian rhythm of blood pressure during normal pregnancy and pregnancies complicated by chronic hypertension and preeclampsia warrant consideration when monitoring patients and implementing management plans.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71412/1/j.1552-6909.2000.tb02771.x.pd

Adiposity and hepatic lipid in healthy full-term, breastfed, and formula-fed human infants: a prospective short-term longitudinal cohort study

Background: The effect of mode of infant feeding on adiposity deposition is not fully understood. Objective: The objective was to test the hypothesis that differences in total and regional adipose tissue content and intrahepatocellular lipid (IHCL) arise in early infancy between breast- and formula-fed infants and to describe longitudinal changes. Design: This prospective longitudinal cohort study was performed in 2 hospitals in the United Kingdom. Healthy, full-term, appropriate weight-for-gestational age infants were recruited; adipose tissue volume and distribution were directly quantified by using whole-body magnetic resonance imaging; IHCL was assessed by in vivo proton magnetic resonance spectroscopy. Measurements were performed after birth (median age: 13 d) and at 6–12 wk of age. Method of infant feeding was recorded prospectively by using maternally completed feeding diaries. Breastfed was defined as >80% of feeds consisting of breast milk at both points; formula-fed was defined as >80% of feeds consisting of formula milk at both points. Results: Longitudinal results were obtained from 70 infants (36 breastfed, 9 mixed-fed, and 25 formula-fed). No differences were found in total or regional adipose tissue or IHCL between breastfed and formula-fed infants. In pooled analyses including all feeding groups, IHCL and total adipose tissue approximately doubled between birth and 6–12 wk: IHCL after birth (median: 0.949; IQR: 0.521–1.711) and at 6–12 wk (1.828; 1.376–2.697; P < 0.001) and total adipose tissue after birth (0.749 L; 0.620–0.928 L) and at 6–12 wk (1.547 L; 1.332–1.790 L; P < 0.001). Increasing adiposity was characterized by greater relative increases in subcutaneous than in internal adipose tissue depots. Conclusions: No differences were detectable in adipose tissue or IHCL accretion between breastfed and formula-fed infants up to 2 mo. The substantial increase in IHCL seen over this period in both breastfed and formula-fed infants is a novel observation, which suggests that hepatic storage of lipids may be physiologic up to 2 mo. This trial was registered at www.clinicaltrials.gov as NCT02033005

ARE EXPOSURE PREDICTIONS, USED FOR THE PRIORITISATION OF PHARMACEUTICALS IN THE ENVIRONMENT, FIT FOR PURPOSE?

Prioritisation methodologies are often used for identifying those pharmaceuticals that pose the greatest risk to the natural environment and to focus laboratory testing or environmental monitoring towards pharmaceuticals of greatest concern. Risk-based prioritisation approaches, employing models to derive exposure concentrations, are commonly used but the reliability of these models is unclear. The present study evaluated the accuracy of exposure models commonly used for pharmaceutical prioritisation. Targeted monitoring was conducted for 95 pharmaceuticals in the Rivers Foss and Ouse in the City of York, UK. Predicted environmental concentration (PEC) ranges were estimated based on localised prescription, hydrological data, reported metabolism and wastewater treatment plant (WwTP) removal rates, and were compared to measured environmental concentrations (MECs). For the River Foss, PECs, obtained using highest metabolism and lowest WwTP removal, were similar to MECs. In contrast, this trend was not observed for the River Ouse, possibly due to pharmaceutical inputs beyond our modelling. Pharmaceuticals were ranked by risk based on either MECs or PECs. With two exceptions (dextromethorphan and diphenhydramine), risk ranking based on both MECs and PECs produced similar results in the River Foss. Overall, these findings indicate that PECs may well be appropriate for prioritisation of pharmaceuticals in the environment when robust and local data on the system of interest are available and reflective of most source inputs to the system. This article is protected by copyright. All rights reserved

Post-translational regulation of retinal IMPDH1 in vivo to adjust GTP synthesis to illumination conditions

We report the in vivo regulation of Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1) in the retina. IMPDH1 catalyzes the rate-limiting step in the de novo synthesis of guanine nucleotides, impacting the cellular pools of GMP, GDP and GTP. Guanine nucleotide homeostasis is central to photoreceptor cells, where cGMP is the signal transducing molecule in the light response. Mutations in IMPDH1 lead to inherited blindness. We unveil a light-dependent phosphorylation of retinal IMPDH1 at Thr159/Ser160 in the Bateman domain that desensitizes the enzyme to allosteric inhibition by GDP/GTP. When exposed to bright light, living mice increase the rate of GTP and ATP synthesis in their retinas; concomitant with IMPDH1 aggregate formation at the outer segment layer. Inhibiting IMPDH activity in living mice delays rod mass recovery. We unveil a novel mechanism of regulation of IMPDH1 in vivo, important for understanding GTP homeostasis in the retina and the pathogenesis of adRP10 IMPDH1 mutations

Epitaxial growth of perovskite oxide films facilitated by oxygen vacancies

The authors would like to thank P. Yudin for valuable discussions, N. Nepomniashchaia for VASE studies, and S. Cichon for XPS analysis. The authors acknowledge support from the Czech Science Foundation (Grant No. 19-09671S), the European Structural and Investment Funds and the Ministry of Education, Youth and Sports of the Czech Republic through Programme ‘‘Research, Development and Education’’ (Project No. SOLID21 CZ.02.1.01/0.0/0.0/16-019/0000760), and ERA NET project Sun2Chem (E. K. and L. R.). Calculations have been done on the LASC Cluster in the ISSP UL.Single-crystal epitaxial films of technologically important and scientifically intriguing multifunctional ABO3 perovskite-type metal oxides are essential for advanced applications and understanding of these materials. In such films, a film-substrate misfit strain enables unprecedented crystal phases and unique properties that are not available in their bulk counterparts. However, the prerequisite growth of strained epitaxial films is fundamentally restricted by misfit relaxation. Here we demonstrate that introduction of a small oxygen deficiency concurrently stabilizes epitaxy and increases lattice strain in thin films of archetypal perovskite oxide SrTiO3. By combining experimental and theoretical methods, we found that lattice distortions around oxygen vacancies lead to anisotropic local stresses, which interact with the misfit strain in epitaxial films. Consequently, specific crystallographic alignments of the stresses are energetically favorable and can facilitate epitaxial growth of strained films. Because anisotropic oxygen-vacancy stresses are inherent to perovskite-type and many other oxides, we anticipate that the disclosed phenomenon of epitaxial stabilization by oxygen vacancies is relevant for a very broad range of functional oxides.This work is licensed under CC BY, CC BY-NC licenses.Czech Science Foundation (Grant No. 19-09671S); European Structural and Investment Funds and the Ministry of Education, Youth and Sports of the Czech Republic through Programme ‘‘Research, Development and Education’’ (Project No. SOLID21 CZ.02.1.01/0.0/0.0/16-019/0000760), and ERA NET project Sun2Chem; Institute of Solid State Physics, University of Latvia as the Center of Excellence has received funding from the European Union’s Horizon 2020 Framework Programme H2020-WIDESPREAD-01-2016-2017-TeamingPhase2 under grant agreement No. 739508, project CAMART²

Corrigendum to "European Society for Vascular Surgery (ESVS) 2022 Clinical Practice Guidelines on the Management of Chronic Venous Disease of the Lower Limbs. [Eur J Vasc Endovasc Surg (2022) 63, 184-267]"

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Modelling study of soil C, N and pH response to air pollution and climate change using European LTER site observations

Current climate warming is expected to continue in coming decades, whereas high N deposition may stabilize, in contrast to the clear decrease in S deposition. These pressures have distinctive regional patterns and their resulting impact on soil conditions is modified by local site characteristics. We have applied the VSD+ soil dynamic model to study impacts of deposition and climate change on soil properties, using MetHyd and GrowUp as pre-processors to provide input to VSD+. The single-layer soil model VSD+ accounts for processes of organic C and N turnover, as well as charge and mass balances of elements, cation exchange and base cation weathering. We calibrated VSD+ at 26 ecosystem study sites throughout Europe using observed conditions, and simulated key soil properties: soil solution pH (pH), soil base saturation (BS) and soil organic carbon and nitrogen ratio (C:N) under projected deposition of N and S, and climate warming until 2100. The sites are forested, located in the Mediterranean, forested alpine, Atlantic, continental and boreal regions. They represent the long-term ecological research (LTER) Europe network, including sites of the ICP Forests and ICP Integrated Monitoring (IM) programmes under the UNECE Convention on Long-range Transboundary Air Pollution (LRTAP), providing high quality long-term data on ecosystem response. Simulated future soil conditions improved under projected decrease in deposition and current climate conditions: higher pH, BS and C:N at 21, 16 and 12 of the sites, respectively. When climate change was included in the scenario analysis, the variability of the results increased. Climate warming resulted in higher simulated pH in most cases, and higher BS and C:N in roughly half of the cases. Especially the increase in C:N was more marked with climate warming. The study illustrates the value of LTER sites for applying models to predict soil responses to multiple environmental changes

Editor's Choice – European Society for Vascular Surgery (ESVS) 2022 Clinical Practice Guidelines on the Management of Chronic Venous Disease of the Lower Limbs

Corrigendum: Volume 64, Issues 2–3, 2022, 284-285Peer reviewe

A Phase I study of the angiogenesis inhibitor SU5416 (semaxanib) in solid tumours, incorporating dynamic contrast MR pharmacodynamic end points

SU5416 (Z-3-[(2,4-dimethylpyrrol-5-yl)methylidenyl]-2-indolinone; semaxanib) is a small molecule inhibitor of the vascular endothelial growth factor receptor (VEGFR)2. A Phase I dose escalation study was performed. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used as a pharmacodynamic assessment tool. In all, 27 patients were recruited. SU5416 was administered twice weekly by fixed rate intravenous infusion. Patients were treated in sequential cohorts of three patients at 48, 65, 85 110 and 145 mg m−2. A further dose level of 190 mg m−2 after a 2-week lead in period at a lower dose was completed; thereafter, the cohort at 145 mg m−2 was expanded. SU5416 showed linear pharmacokinetics to 145 mg m−2 with a large volume of distribution and rapid clearance. A significant degree of interpatient variability was seen. SU5416 was well tolerated, by definition a maximum-tolerated dose was not defined. No reproducible changes were seen in DCE-MRI end points. Serial assessments of VEGF in a cohort of patients treated at 145 mg m−2 did not show a statistically significant treatment-related change. Parallel assessments of the impact of SU5416 on coagulation profiles in six patients showed a transient effect within the fibrinolytic pathway. Clinical experience showed that patients who had breaks of therapy longer than a week could not have treatment reinitiated at a dose of 190 mg m−2 without unacceptable toxicity. The 145 mg m−2 dose level is thus the recommended dose for future study