Publications by authors named "Ian Williams"

487 Publications

The fate of the left subclavian artery in TEVAR for aortic arch pathology.

J Card Surg 2021 Jul 26. Epub 2021 Jul 26.

Department of Vascular Surgery, University Hospital of Wales, Heath Park, Cardiff, UK.

Background And Aim Of Study: The origin of the vertebral artery (VA) from the left subclavian (LSA) is variable and must be considered when proximal ligation or embolization is performed post thoracic endovascular aortic repair (TEVAR) and extra-anatomical bypass (EAB). A retrospective study was conducted to understand the patency of the LSA and VAs after TEVAR and the relationship of the EAB to the LSA.

Methods: Fifty-six patients underwent TEVAR where the LSA origin was occluded. A comparison was performed between the length of the proximal LSA from the arch of the aorta to the origin of the VA. Patient outcomes included posterior or anterior circulation cerebrovascular accident, spinal cord ischemia (SCI), and symptoms and signs of left arm ischemia (LAI). Thirty one underwent EAB with 8 undergoing occlusion of the LSA proximal to the origin of the left VA. A further 25 underwent TEVAR with no EAB performed. The mean (standard deviation) of origin of the VA from the origin at the arch was 37.0 (12.9) mm compared to 34.0 (13.7) mm in those where no bypass was performed (p 0.45). Four patients underwent intraluminal plug occlusion and four had external ligation of the proximal LSA in those undergoing EAB.

Conclusions: Careful evaluation of the LSA is needed when planning TEVAR as occlusion techniques may be dependent on a minimum length of the VA from the aortic arch. The mean length of the VA from the aorta has high heterogeneity which may dictate the optimum occlusion method for LSA.
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http://dx.doi.org/10.1111/jocs.15831DOI Listing
July 2021

Impact of pharmacist and physician collaborations in primary care on reducing readmission to hospital: A systematic review and meta-analysis.

Res Social Adm Pharm 2021 Jul 16. Epub 2021 Jul 16.

School of Pharmacy, The University of Queensland, Woolloongabba, Australia.

Background: Readmissions to hospital due to medication-related problems are common and may be preventable. Pharmacists act to optimise use of medicines during care transitions from hospital to community.

Objective: To assess the impact of pharmacist-led interventions, which include communication with a primary care physician (PCP) on reducing hospital readmissions.

Methods: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL and Web of Science were searched for articles published from inception to March 2021 that described interventions involving a pharmacist interacting with a PCP in regards to medication management of patients recently discharged from hospital. The primary outcome was effect on all-cause readmission expressed as Mantel-Haenszel risk ratio (RR) derived from applying a random effects model to pooled data. Sensitivity analysis was also conducted to investigate differences between randomised controlled trials (RCTs) and non-RCTs. The GRADE system was applied in rating the quality of evidence and certainty in the estimates of effect.

Results: In total, 37 studies were included (16 RCTs and 29 non-RCTs). Compared to control patients, the proportion of intervention patients readmitted at least once was significantly reduced by 13% (RR = 0.87, CI:0.79-0.97, p = 0.01; low to very low certainty of evidence) over follow-up periods of variable duration in all studies combined, and by 22% (RR = 0.78, CI:0.67-0.92; low certainty of evidence) at 30 day follow-up across studies reporting this time point. Analysis of data from RCTs only showed no significant reduction in readmissions (RR = 0.92, CI:0.80-1.06; low certainty of evidence).

Conclusions: The totality of evidence suggests pharmacist-led interventions with PCP communication are effective in reducing readmissions, especially at 30 days follow-up. Future studies need to adopt more rigorous study designs and apply well-defined patient eligibility criteria.
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http://dx.doi.org/10.1016/j.sapharm.2021.07.015DOI Listing
July 2021

How Do Molecular Motions Affect Structures and Properties at Molecule and Aggregate Levels?

J Am Chem Soc 2021 Jul 22. Epub 2021 Jul 22.

Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction and Institute for Advanced Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong 999077, China.

Molecular motions are essential natures of matter and play important roles in their structures and properties. However, owing to the diversity and complexity of structures and behaviors, the study of motion-structure-property relationships remains a challenge, especially at all levels of structural hierarchy from molecules to macro-objects. Herein, luminogens showing aggregation-induced emission (AIE), namely, 9-(pyrimidin-2-yl)-carbazole (PyCz) and 9-(5-R-pyrimidin-2-yl)-carbazole [R = Cl (ClPyCz), Br (BrPyCz), and CN (CyPyCz)], were designed and synthesized, to decipher the dependence of materials' structures and properties on molecular motions at the molecule and aggregate levels. Experimental and theoretical analysis demonstrated that the active intramolecular motions in the excited state of all molecules at the single-molecule level endowed them with more twisted structural conformations and weak emission. However, owing to the restriction of intramolecular motions in the nano/macroaggregate state, all the molecules assumed less twisted conformations with bright emission. Unexpectedly, intermolecular motions could be activated in the macrocrystals of ClPyCz, BrPyCz, and CyPyCz through the introduction of external perturbations, and synergic strong and weak intermolecular interactions allowed their crystals to undergo reversible deformation, which effectively solved the problem of the brittleness of organic crystals, while endowing them with excellent elastic performance. Thus, the present study provided insights on the motion-structure-property relationship at each level of structural hierarchy and offered a paradigm to rationally design multifunctional AIE-based materials.
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http://dx.doi.org/10.1021/jacs.1c05647DOI Listing
July 2021

Associations between plasma nucleoside reverse transcriptase inhibitors concentrations and cognitive function in people with HIV.

PLoS One 2021 21;16(7):e0253861. Epub 2021 Jul 21.

Department of Infectious Disease, Imperial College London, London, United Kingdom.

Objectives: To investigate the associations of plasma lamivudine (3TC), abacavir (ABC), emtricitabine (FTC) and tenofovir (TFV) concentrations with cognitive function in a cohort of treated people with HIV (PWH).

Methods: Pharmacokinetics (PK) and cognitive function (Cogstate, six domains) data were obtained from PWH recruited in the POPPY study on either 3TC/ABC or FTC/tenofovir disoproxil fumarate (TDF)-containing regimens. Association between PK parameters (AUC0-24: area under the concentration-time curve over 24 hours, Cmax: maximum concentration and Ctrough: trough concentration) and cognitive scores (standardized into z-scores) were evaluated using rank regression adjusting for potential confounders.

Results: Median (IQR) global cognitive z-scores in the 83 PWH on 3TC/ABC and 471 PWH on FTC/TDF were 0.14 (-0.27, 0.38) and 0.09 (-0.28, 0.42), respectively. Higher 3TC AUC0-24 and Ctrough were associated with better global z-scores [rho = 0.29 (p = 0.02) and 0.27 (p = 0.04), respectively], whereas higher 3TC Cmax was associated with poorer z-scores [rho = -0.31 (p<0.01)], independently of ABC concentrations. Associations of ABC PK parameters with global and domain z-scores were non-significant after adjustment for confounders and 3TC concentrations (all p's>0.05). None of the FTC and TFV PK parameters were associated with global or domain cognitive scores.

Conclusions: Whilst we found no evidence of either detrimental or beneficial effects of ABC, FTC and TFV plasma exposure on cognitive function of PWH, higher plasma 3TC exposures were generally associated with better cognitive performance although higher peak concentrations were associated with poorer performance.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253861PLOS
July 2021

Endocardial/endothelial angiocrines regulate cardiomyocyte development and maturation and induce features of ventricular non-compaction.

Eur Heart J 2021 Jul 19. Epub 2021 Jul 19.

Department of Biology, Stanford University, Stanford, CA 94305, USA.

Aims: Non-compaction cardiomyopathy is a devastating genetic disease caused by insufficient consolidation of ventricular wall muscle that can result in inadequate cardiac performance. Despite being the third most common cardiomyopathy, the mechanisms underlying the disease, including the cell types involved, are poorly understood. We have previously shown that endothelial cell-specific deletion of the chromatin remodeller gene Ino80 results in defective coronary vessel development that leads to ventricular non-compaction in embryonic mouse hearts. We aimed to identify candidate angiocrines expressed by endocardial and ECs inwildtype and LVNC conditions in Tie2Cre;Ino80fl/fl transgenic embryonic mouse hearts, and test the effect of these candidates on cardiomyocyte proliferation and maturation.

Methods And Results: We used single-cell RNA-sequencing to characterize endothelial and endocardial defects in Ino80-deficient hearts. We observed a pathological endocardial cell population in the non-compacted hearts and identified multiple dysregulated angiocrine factors that dramatically affected cardiomyocyte behaviour. We identified Col15A1 as a coronary vessel-secreted angiocrine factor, downregulated by Ino80-deficiency, that functioned to promote cardiomyocyte proliferation. Furthermore, mutant endocardial and endothelial cells (ECs) up-regulated expression of secreted factors, such as Tgfbi, Igfbp3, Isg15, and Adm, which decreased cardiomyocyte proliferation and increased maturation.

Conclusions: These findings support a model where coronary ECs normally promote myocardial compaction through secreted factors, but that endocardial and ECs can secrete factors that contribute to non-compaction under pathological conditions.
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http://dx.doi.org/10.1093/eurheartj/ehab298DOI Listing
July 2021

Unusual light-driven amplification through unexpected regioselective photogeneration of five-membered azaheterocyclic AIEgen.

Chem Sci 2020 Oct 19;12(2):709-717. Epub 2020 Oct 19.

Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, State Key Laboratory of Molecular Nanoscience, Division of Life Science, Department of Chemical and Biomedical Engineering and Institute for Advanced Study, The Hong Kong University of Science and Technology Clear Water Bay Kowloon Hong Kong China

Developing versatile synthetic methodologies with merits of simplicity, efficiency, and environment friendliness for five-membered heterocycles is of incredible importance to pharmaceutical and material science, as well as a huge challenge to synthetic chemistry. Herein, an unexpected regioselective photoreaction to construct a fused five-membered azaheterocycle with an aggregation-induced emission (AIE) characteristic is developed under mild conditions. The formation of the five-membered ring is both thermodynamically and kinetically favored, as justified by theoretical calculation and experimental evidence. Markedly, a light-driven amplification strategy is proposed and applied in selective mitochondria-targeted cancer cell recognition and fluorescent photopattern fabrication with improved resolution. The work not only delivers the first report on efficiently generating a fused five-membered azaheterocyclic AIE luminogen under mild conditions photoreaction, but also offers deep insight into the essence of the photosynthesis of fused five-membered azaheterocyclic compounds.
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http://dx.doi.org/10.1039/d0sc04725bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179000PMC
October 2020

Visualization and Manipulation of Solid-State Molecular Motions in Cocrystallization Processes.

J Am Chem Soc 2021 Jun 21;143(25):9468-9477. Epub 2021 Jun 21.

Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Department of Chemical and Biomedical Engineering, Institute for Advanced Study, and Guangdong Hong Kong Macro Joint Laboratory of Optoelectronic and Magnetic Functional Materials, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.

Solid-state molecular motions (SSMM) play a critical role in adjusting behaviors and properties of materials. However, research on SSMM, especially for multicomponent systems, suffers from various problems and is rarely explored. Herein, through collaboration with cocrystal engineering, visualization and manipulation of SSMM in two-component systems, namely, FSBO (()-2-(4-fluorostyryl)benzo[]oxazole)/TCB (1,2,4,5-tetracyanobenzene) and PVBO (()-2-(2-(pyridin-4-yl)vinyl)benzo[]oxazole)/TCB, were realized. The obtained yellow-emissive F/T (FSBO/TCB) cocrystal displayed turn-on fluorescence, and the green-emissive P/T (PVBO/TCB) cocrystal presented redder emission, both of which exhibited an aggregation-induced emission property. At varied pressure and temperature, the grinding mixtures of FSBO/TCB and PVBO/TCB displayed different molecular motions that were readily observed through the fluorescence signal. Notably, even without grinding, FSBO and TCB molecules could move over for 4 mm in a 1D tube. The unique emission changes induced by SSMM were applied in information storage and dynamic anticounterfeiting. This work not only visualized and manipulated SSMM but offered more insights for multicomponent study in aggregate science.
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http://dx.doi.org/10.1021/jacs.1c02594DOI Listing
June 2021

How to Manipulate Through-Space Conjugation and Clusteroluminescence of Simple AIEgens with Isolated Phenyl Rings.

J Am Chem Soc 2021 Jun 11;143(25):9565-9574. Epub 2021 Jun 11.

Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction and Institute for Advanced Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong 999077, China.

Apart from the traditional through-bond conjugation (TBC), through-space conjugation (TSC) is gradually proved as another important interaction in photophysical processes, especially for the recent observation of clusteroluminescence from nonconjugated molecules. However, unlike TBC in conjugated chromophores, it is still challenging to manipulate TSC and clusteroluminescence. Herein, simple and nonconjugated triphenylmethane (TPM) and its derivatives with electron-donating and electron-withdrawing groups were synthesized, and their photophysical properties were systematically studied. TPM was characterized with visible clusteroluminescence due to the intramolecular TSC. Experimental and theoretical results showed that the introduction of electron-donating groups into TPM could red-shift the wavelength and increase the efficiency of clusteroluminescence simultaneously, due to the increased electronic density and stabilization of TSC. However, TPM derivatives with electron-withdrawing groups showed inefficient or even quenched clusteroluminescence caused by the vigorous excited-state intramolecular motion and intermolecular photoinduced electron transfer process. This work provides a reliable strategy to manipulate TSC and clusteroluminescence.
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http://dx.doi.org/10.1021/jacs.1c03882DOI Listing
June 2021

Varying degrees of homostructurality in a series of cocrystals of antimalarial drug 11-azaartemisinin with salicylic acids.

Acta Crystallogr C Struct Chem 2021 06 6;77(Pt 6):262-270. Epub 2021 May 6.

Department of Chemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, People's Republic of China.

The X-ray structures of three new 1:1 pharmaceutical cocrystals of 11-azaartemisinin (11-Aza; systematic name: 1,5,9-trimethyl-14,15,16-trioxa-11-azatetracyclo[10.3.1.0.0]hexadecan-10-one, CHNO) with bromo-substituted salicylic acids [namely, 5-bromo- (5-BrSalA, CHBrO), 4-bromo- (4-BrSalA, CHBrO) and 3,5-dibromosalicylic acid (3,5-BrSalA, CHBrO)] are reported. All the structures are related to the parent 11-Aza:SalA cocrystal (monoclinic P2) reported previously. The 5-BrSalA analogue is isostructural with the parent, with lattice expansion along the c axis. The 4-BrSalA and 3,5-BrSalA cocrystals retain the highly preserved 2 stacks of the molecular pairs, but these pack with a varying degree of slippage with respect to neighbouring stacks, altering the close contacts between them, and represent two potential alternative homostructural arrangements for the parent compound. Structure redeterminations of the bromosalicylic acids 5-BrSalA, 4-BrSalA and 3,5-BrSalA at 100 K show that the packing efficiency of the cocrystals need not be higher than the parent coformers, based on specific-volume calculations, attributable to the strong O-H...O=C hydrogen bonds of 2.54 Å in the cocrystals.
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http://dx.doi.org/10.1107/S2053229621004460DOI Listing
June 2021

Synthesis, structure and reactivity of iridium complexes containing a bis-cyclometalated tridentate C^N^C ligand.

Dalton Trans 2021 Jun;50(24):8512-8523

Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.

In an effort to synthesize cyclometalated iridium complexes containing a tridentate C^N^C ligand, transmetallation of [Hg(HC^N^C)Cl] (1) (H2C^N^C = 2,6-bis(4-tert-butylphenyl)pyridine) with various organoiridium starting materials has been studied. The treatment of 1 with [Ir(cod)Cl]2 (cod = 1,5-cyclooctadiene) in acetonitrile at room temperature afforded a hexanuclear Ir4Hg2 complex, [Cl(κ2C,N-HC^N^C)(cod)IrHgIr(cod)Cl2]2 (2), which features Ir-Hg-Ir and Ir-Cl-Ir bridges. Refluxing 2 with sodium acetate in tetrahydrofuran (thf) resulted in cyclometalation of the bidentate HC^N^C ligand and formation of trinuclear [(C^N^C)(cod)IrHgIr(cod)Cl2] (3). On the other hand, refluxing [Ir(cod)Cl]2 with 1 and sodium acetate in thf yielded [Ir(C^N^C)(cod)(HgCl)] (4). Chlorination of 4 with PhICl2 gave [Ir(C^N^C)(cod)Cl]·HgCl2 (5·HgCl2) that reacted with tricyclohexylphosphine to yield Hg-free [Ir(C^N^C)(cod)Cl] (5). Chloride abstraction of 5 with silver(i) triflate (AgOTf) gave [Ir(C^N^C)(cod)(H2O)](OTf) (6) that can catalyze the cyclopropanation of styrene with ethyl diazoacetate. Reaction of 1 and [Ir(CO)2Cl(py)] (py = pyridine) with sodium acetate in refluxing thf afforded [Ir(C^N^C)(HgCl)(py)(CO)] (7), in which the carbonyl ligand is coplanar with the C^N^C ligand. On the other hand, refluxing 1 with (PPh4)[Ir(CO)2Cl2] and sodium acetate in acetonitrile gave [Ir(C^N^C)(κ2C,N-HC^N^C)(CO)] (8), the carbonyl ligand of which is trans to the pyridyl ring of the bidentate HC^N^C ligand. Upon irradiation with UV light 8 in thf was isomerized to 8', in which the carbonyl is trans to a phenyl group of the bidentate HC^N^C ligand. The isomer pair 8 and 8' exhibited emission at 548 and 514 nm in EtOH/MeOH at 77 K with lifetime of 84.0 and 64.6 μs, respectively. Protonation of 8 with p-toluenesulfonic acid (TsOH) afforded the bis(bidentate) tosylate complex [Ir(κ2C,N-HC^N^C)2(CO)(OTs)] (9) that could be reconverted to 8 upon treatment with sodium acetate. The electrochemistry of the Ir(C^N^C) complexes has been studied using cyclic voltammetry. Reaction of [Ir(PPh3)3Cl] with 1 and sodium acetate in refluxing thf led to isolation of the previously reported compound [Ir(κ2P,C-C6H4PPh2)2(PPh3)Cl] (10). The crystal structures of 2-5, 8, 8', 9 and 10 have been determined.
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http://dx.doi.org/10.1039/d1dt01269jDOI Listing
June 2021

An Air-Stable Organic Radical from a Controllable Photoinduced Domino Reaction of a Hexa-aryl Substituted Anthracene.

J Org Chem 2021 Jun 25;86(11):7359-7369. Epub 2021 May 25.

Department of Chemistry, The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Institute for Advanced Study, Department of Chemical and Biological Engineering, Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.

Air-stable organic radicals and radical ions have attracted great attention for their far-reaching application ranging from bioimaging to organic electronics. However, because of the highly reactive nature of organic radicals, the design and synthesis of air-stable organic radicals still remains a challenge. Herein, an air-stable organic radical from a controllable photoinduced domino reaction of a hexa-aryl substituted anthracene is described. The domino reaction involves a photoinduced [4 + 2] cycloaddition reaction, rearrangement, photolysis, and an elimination reaction; H/C NMR spectroscopy, high resolution mass spectrometry, single-crystal X-ray diffraction, and EPR spectroscopy were exploited for characterization. Furthermore, a photoinduced domino reaction mechanism is proposed according to the experimental and theoretical studies. In addition, the effects of employing push and pull electronic groups on the controllable photoinduced domino reaction were investigated. This article not only offers a new blue emitter and novel air-stable organic radical compound for potential application in organic semiconductor applications, but also provides a perspective for understanding the fundamentals of the reaction mechanism on going from anthracene to semiquinone in such anthracene systems.
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http://dx.doi.org/10.1021/acs.joc.1c00233DOI Listing
June 2021

Daily GnRH agonist treatment delays the development of reproductive physiology and behavior in male rats.

Horm Behav 2021 Jun 3;132:104982. Epub 2021 May 3.

Division of Pharmacology and Toxicology, The University of Texas, at Austin, Austin, TX 78712, USA.

The present study was designed to examine the effects of suppressing pubertal onset with leuprolide acetate, a gonadotropin releasing hormone (GnRH) agonist. Starting on postnatal day (PD) 25, male Long-Evans rats were injected daily with either leuprolide acetate (25 μg/kg dissolved in 0.9% sterile physiological saline; n = 13) or sterile physiological saline (1.0 ml/kg 0.9% NaCl; n = 14) for a total of 25 days. Males were monitored daily for signs of puberty (i.e., preputial separation). On the last day of leuprolide treatment (PD 50), half of each treatment group was injected with 10.0 μg of estradiol benzoate (EB) daily for three consecutive days (PD 50-52) and 1.0 mg of progesterone (P) on the 4th day (PD 53), whereas the other half of each treatment group received oil injections. Four hours after P injections, all subjects were given the opportunity to interact with a gonadally-intact male and a sexually receptive female rat (i.e., a partner-preference test with and without physical contact). Copulatory behavior and sexual motivation were measured. Hormone injections and mating tests were repeated weekly for a total of 3 consecutive weeks. Results showed that leuprolide delayed puberty as well as the development of copulatory behavior and the expression of sexual motivation. By the last test, the leuprolide-treated subjects showed signs of catching up, however, many continued to be delayed. Estradiol and progesterone mildly feminized male physiology (e.g., decreased testes weight and serum testosterone) and behavior (e.g., increased lordosis), but did not interact with leuprolide treatment.
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http://dx.doi.org/10.1016/j.yhbeh.2021.104982DOI Listing
June 2021

Renal Arteries Revisited: Anatomy, Pathologic Entities, and Implications for Endovascular Management.

Radiographics 2021 May-Jun;41(3):909-928

From the Departments of Radiology (R.D.W., K.S.M., M.G.S., W.R.T., A.C.G., A.M.W.) and Vascular Surgery (I.M.W.), University Hospital of Wales, Heath Park, Cardiff CF14 4XW, Wales; and Department of Radiology, Ninewells Hospital and Medical School, Dundee, Scotland (I.A.Z.).

The renal arteries (RAs) are important vessels that usually arise from the abdominal aorta and supply the kidneys; thus, these arteries play a vital role in physiologic functions such as hemofiltration and blood pressure regulation. An understanding of the basis for embryologic development and the frequently variable anatomy of the RAs is necessary to fully appreciate the range of diseases and the implications for procedural planning. Hemorrhage from an RA is relatively common and is typically traumatic or spontaneous, with the latter form often seen in association with underlying tumors or arteriopathy. Accurate diagnostic evaluation of RA disease due to conditions such as atherosclerosis, fibromuscular dysplasia, vasculitis, aneurysm, arteriovenous shunt, embolic disease, and dissection is dependent on the use of multimodality imaging and is essential for selecting appropriate clinical management, with endovascular therapy having a key role in treatment. Surgical considerations include extra-anatomic renal bypass, which remains an important treatment option even in this era of endovascular therapy, and RA embolization as an adjunct to tumor surgery. A novel area of research interest is the potential role of RA denervation in the management of refractory hypertension. RSNA, 2021.
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http://dx.doi.org/10.1148/rg.2021200162DOI Listing
May 2021

Developing a systematic method for extraction of microplastics in soils.

Anal Methods 2021 04 22;13(14):1695-1705. Epub 2021 Mar 22.

Faculty of Engineering and Physical Sciences, University of Southampton, Highfield Campus, University Road, Southampton SO17 1BJ, UK.

Microplastics are an environmental issue of global concern. Although they have been found in a range of environments worldwide, their contamination in the terrestrial environment is poorly understood. The lack of standardised methods for their detection and quantification is a major obstacle for determining the risk they pose to soil environments. Here we present a systematic comparison of microplastic extraction methods from soils, taking into account the characteristics of the soil medium to determine the best methods for quantification. The efficiency of organic matter removal using hydrogen peroxide, potassium hydroxide and Fenton's reagent was measured. Soils with a range of particle size distribution and organic matter content were spiked with a variety of microplastic types. Density separation methods using sodium chloride, zinc chloride and canola oil were tested. Recovery efficiencies were calculated and the impact of the reagents on the microplastics was quantified using Attenuated Total Reflectance (ATR) Fourier Transform-Infrared (FTIR) spectroscopy. The optimal organic removal method was found to be hydrogen peroxide. The recovery efficiency of microplastics was variable across polymer types. Overall, canola oil was shown to be the optimal method for density separation, however, efficiency was dependent on the amount of organic matter in the soil. This outcome highlights the importance of including matrix-specific calibration in future studies considering a wide range of microplastic types, to avoid underestimation of microplastic contamination. We show here that methods for extracting microplastics from soils can be simple, cost-effective and widely applicable, which will enable the advancement of microplastic research in terrestrial environments.
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http://dx.doi.org/10.1039/d0ay02086aDOI Listing
April 2021

When is extra-anatomical bypass for the left subclavian artery required to prevent ischaemia after thoracic endovascular stent grafting?

Asian Cardiovasc Thorac Ann 2021 Jul 4;29(6):524-531. Epub 2021 Apr 4.

Regional Vascular Unit, University Hospital of Wales, Cardiff, UK.

Introduction: Thoracic endovascular aortic repair (TEVAR) has become an accepted treatment for thoracic aortic disease. However, the principal complications relate to coverage of the thoracic aortic wall and deliberate occlusion of aortic branches over a potentially long segment. Complications include risk of stroke, spinal cord ischaemia (SCI) and arterial insufficiency to the left arm (left arm ischaemia (LAI)). This study specifically scrutinised the development of SCI and LAI after TEVAR for interventions for thoracic aortic disease from 1999 to 2020. In particular, those who underwent extra-anatomical bypass (both immediate and late) were compared to the length of thoracic aortic coverage by the stent graft.

Materials And Methods: Ninety-eight patients underwent TEVAR. The presenting symptoms, pathology, procedural and follow-up data were collected prospectively with particular evidence of stroke, SCI and LAI both immediate onset and after 48 h of graft placement.

Results: Fifty underwent TEVAR for an aneurysm (thoracoabdominal aortic aneurysm), 22 for dissection, 19 for acute transection and 7 for intramural haematoma/pseudoaneurysm of the thoracic aorta. Twenty-nine (30%) required a debranching procedure to increase the proximal landing zone (1 aorto-carotid subclavian bypass, 10 carotid/carotid subclavian bypass and 18 carotid/subclavian bypass). Ten patients (10%) died within 30 days of TEVAR. Twenty-four grafts covered the left subclavian artery origin without a carotid/subclavian bypass. Five required a delayed carotid/subclavian bypass for LAI (4) and SCI (1). Six developed immediate signs of SCI after TEVAR and these 11 (group i) had a mean (SD) length of coverage of the thoracic aorta of 30.2 (10.6) cm compared to 21.5 (11.2) cm (group g) in those who had no LAI or SCI post TEVAR,  < 0.05.

Conclusions: In this series, delayed carotid/subclavian bypass may be required for chronic arm ischaemia and less so for SCI. The length of coverage of thoracic aorta during TEVAR is a factor in the development of delayed SCI and LAI occurrence. Carotid subclavian bypass is required for certain patients undergoing TEVAR (particularly if greater than 20 cm of thoracic aorta is covered).
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http://dx.doi.org/10.1177/02184923211008074DOI Listing
July 2021

Disability Outcomes in the N-MOmentum Trial of Inebilizumab in Neuromyelitis Optica Spectrum Disorder.

Neurol Neuroimmunol Neuroinflamm 2021 05 26;8(3). Epub 2021 Mar 26.

From the Service de Neurologie Sclérose en Plaques (R.M.), Pathologies de La Myéline et Neuro-inflammation, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, France; University of Colorado School of Medicine (J.L.B.), Anschutz Medical Campus, Aurora; Research Institute and Hospital of National Cancer Center (H.J.K.), Goyang, South Korea; Mayo Clinic (B.G.W., S.J.P.), Rochester, MN; Mayo Clinic (D.W.), Scottsdale, AZ; Department of Multiple Sclerosis Therapeutics (K.F.), Fukushima Medical University and Multiple Sclerosis and Neuromyelitis Optica Center, Southern Tohoku Research Institute for Neuroscience, Koriyama, Japan; Experimental and Clinical Research Center (F.P.), Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Germany; University of Alabama at Birmingham (G.R.C.); UCSF Weill Institute for Neurosciences (A.J.G.), Department of Neurology and Department of Ophthalmology, University of California San Francisco; Medical Faculty (O.A., H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Icahn School of Medicine at Mount Sinai (F.D.L.), New York; Oxford PharmaGenesis Ltd (I.M.W.), UK; Viela Bio (J.D., D.S., D.C., W.R., M.S., J.N.R., E.K.), Gaithersburg, MD; and UCSF Weill Institute for Neurosciences (B.A.C.C.), University of California San Francisco.

Objective: To assess treatment effects on Expanded Disability Status Scale (EDSS) score worsening and modified Rankin Scale (mRS) scores in the N-MOmentum trial of inebilizumab, a humanized anti-CD19 monoclonal antibody, in participants with neuromyelitis optica spectrum disorder (NMOSD).

Methods: Adults (N = 230) with aquaporin-4 immunoglobulin G-seropositive NMOSD or -seronegative neuromyelitis optica and an EDSS score ≤8 were randomized (3:1) to receive inebilizumab 300 mg or placebo on days 1 and 15. The randomized controlled period (RCP) was 28 weeks or until adjudicated attack, with an option to enter the inebilizumab open-label period. Three-month EDSS-confirmed disability progression (CDP) was assessed using a Cox proportional hazard model. The effect of baseline subgroups on disability was assessed by interaction tests. mRS scores from the RCP were analyzed by the Wilcoxon-Mann-Whitney odds approach.

Results: Compared with placebo, inebilizumab reduced the risk of 3-month CDP (hazard ratio [HR]: 0.375; 95% CI: 0.148-0.952; = 0.0390). Baseline disability, prestudy attack frequency, and disease duration did not affect the treatment effect observed with inebilizumab (HRs: 0.213-0.503; interaction tests: all > 0.05, indicating no effect of baseline covariates on outcome). Mean EDSS scores improved with longer-term treatment. Inebilizumab-treated participants were more likely to have a favorable mRS outcome at the end of the RCP (OR: 1.663; 95% CI: 1.195-2.385; = 0.0023).

Conclusions: Disability outcomes were more favorable with inebilizumab vs placebo in participants with NMOSD.

Classification Of Evidence: This study provides Class II evidence that for patients with NMOSD, inebilizumab reduces the risk of worsening disability. N-MOmentum is registered at ClinicalTrials.gov: NCT02200770.
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http://dx.doi.org/10.1212/NXI.0000000000000978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054974PMC
May 2021

Exploring adolescent and clinician perspectives on Australia.

Aust J Prim Health 2021 Mar 15. Epub 2021 Mar 15.

Adolescence is often a time when risk-taking behaviours emerge and attendance at primary health care is low. School-based health services can serve to improve access to health care. Clinicians play a key role in improving adolescents' health literacy and capacity to make informed care decisions. Australia's national digital health record, My Health Record (MHR), has posed significant challenges for both clinicians and adolescents in understanding impacts on patient privacy. Guidance is required on how best to communicate about MHR to adolescents. This exploratory qualitative study aims to examine adolescents' understanding of MHR, clinicians' knowledge of MHR and their use of MHR with adolescents. Focus groups with students, school health and well-being staff and semistructured interviews with GPs and nurses were undertaken in one regional and one urban secondary school-based health service in Victoria. Transcripts from audio recorded sessions were examined using thematic analysis. Resulting themes include minimal understanding and use of MHR, privacy and security concerns, possible benefits of MHR and convenience. The results suggest opportunities to address gaps in understanding and to learn from adolescents' preferences for digital health literacy education. This will support primary care clinicians to provide best-practice health care for adolescents.
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http://dx.doi.org/10.1071/PY20169DOI Listing
March 2021

Regional carbon stock assessment and the potential effects of land cover change.

Sci Total Environ 2021 Jun 12;775:145815. Epub 2021 Feb 12.

Faculty of Engineering and Physical Sciences, University of Southampton, Highfield Campus, University Road, Southampton SO17 1BJ, United Kingdom. Electronic address:

Accurate assessment of carbon stocks remains a global challenge. High levels of uncertainty in Land Use, Land Use Change and Forestry reporting has hindered decision-makers and investors worldwide to support sustainable soil and vegetation management. Potential mitigation-driven activities and effects are likely to be locally/regionally unique. A spatially-targeted approach is thus required to optimise strategic carbon management. This study provides a new regional carbon assessment (tier 3) approach using biophysical-process modelling of high-resolution Land Cover (LC) data within a UK National Park (NFNP) to provide higher accuracy. Future Land Cover Change (LCC) scenarios were simulated. Vegetation-driven carbon dynamics were modelled by coupling two widely-used models, LPJ-GUESS and RothC-26.3. Transition and persistence analysis was conducted using Terrset's Land Change Modeller to predict likely future LCC for 2040 using Multi-Layer Perceptron Markov-Chain Analysis. Current total carbon in the NFNP is 7.32-8.73 Mt C, with current trajectories of LCC leading to minor losses of up to 0.39 Mt C. Alternative LCC scenarios indicated possible gains or losses of 1.27 Mt C, or 136.7 t C ha. The importance of vegetation-driven carbon storage was greater than the national average, with a VegC pool 12-14% of the soil organic C pool, placing greater significance on local/regional LC and management policy. The potential storage capacity of each LC class was ranked (highest to lowest): Coniferous > Broadleaved/Mixed > Coastal > Semi-natural Grassland > Heath > Improved Grassland > Arable (Cropland). Opportunities were prioritised to inform landscape-scale management to reduce future carbon losses and/or to enhance gains through LCC. Balancing the carbon budget relies upon maintaining existing LC. The more detailed LC classification facilitated accounting of management through stock change factors and disaggregation of classes, achieving greater detail and accuracy. Forthcoming policy decisions must optimise carbon storage at a local/regional landscape-scale.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145815DOI Listing
June 2021

Reducing Medical Admissions and Presentations Into Hospital through Optimising Medicines (REMAIN HOME): a stepped wedge, cluster randomised controlled trial.

Med J Aust 2021 03 12;214(5):212-217. Epub 2021 Feb 12.

University of Queensland, Brisbane, QLD.

Objective: To investigate whether integrating pharmacists into general practices reduces the number of unplanned re-admissions of patients recently discharged from hospital.

Design, Setting: Stepped wedge, cluster randomised trial in 14 general practices in southeast Queensland.

Participants: Adults discharged from one of seven study hospitals during the seven days preceding recruitment (22 May 2017 - 14 March 2018) and prescribed five or more long term medicines, or having a primary discharge diagnosis of congestive heart failure or exacerbation of chronic obstructive pulmonary disease.

Intervention: Comprehensive face-to-face medicine management consultation with an integrated practice pharmacist within seven days of discharge, followed by a consultation with their general practitioner and further pharmacist consultations as needed.

Major Outcomes: Rates of unplanned, all-cause hospital re-admissions and emergency department (ED) presentations 12 months after hospital discharge; incremental net difference in overall costs.

Results: By 12 months, there had been 282 re-admissions among 177 control patients (incidence rate [IR], 1.65 per person-year) and 136 among 129 intervention patients (IR, 1.09 per person-year; fully adjusted IR ratio [IRR], 0.79; 95% CI, 0.52-1.18). ED presentation incidence (fully adjusted IRR, 0.46; 95% CI, 0.22-0.94) and combined re-admission and ED presentation incidence (fully adjusted IRR, 0.69; 95% CI, 0.48-0.99) were significantly lower for intervention patients. The estimated incremental net cost benefit of the intervention was $5072 per patient, with a benefit-cost ratio of 31:1.

Conclusion: A collaborative pharmacist-GP model of post-hospital discharge medicines management can reduce the incidence of hospital re-admissions and ED presentations, achieving substantial cost savings to the health system.

Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12616001627448 (prospective).
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http://dx.doi.org/10.5694/mja2.50942DOI Listing
March 2021

Sensitivity analysis of the primary endpoint from the N-MOmentum study of inebilizumab in NMOSD.

Mult Scler 2021 Feb 4:1352458521988926. Epub 2021 Feb 4.

Viela Bio, Gaithersburg, MD, USA.

Background: In the N-MOmentum trial, the risk of an adjudicated neuromyelitis optica spectrum disorder (NMOSD) attack was significantly reduced with inebilizumab compared with placebo.

Objective: To demonstrate the robustness of this finding, using pre-specified sensitivity and subgroup analyses.

Methods: N-MOmentum is a prospective, randomized, placebo-controlled, double-masked trial of inebilizumab, an anti-CD19 monoclonal B-cell-depleting antibody, in patients with NMOSD. Pre-planned and analyses were performed to evaluate the primary endpoint across a range of attack definitions and demographic groups, as well as key secondary endpoints.

Results: In the N-MOmentum trial (ClinicalTrials.gov: NCT02200770), 174 participants received inebilizumab and 56 received placebo. Attack risk for inebilizumab versus placebo was consistently and significantly reduced, regardless of attack definition, type of attack, baseline disability, ethnicity, treatment history, or disease course (all with hazard ratios < 0.4 favoring inebilizumab, < 0.05). Analyses of secondary endpoints showed similar trends.

Conclusion: N-MOmentum demonstrated that inebilizumab provides a robust reduction in the risk of NMOSD attacks regardless of attack evaluation method, attack type, patient demographics, or previous therapy.The N-MOmentum study is registered at ClinicalTrials.gov: NCT2200770.
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http://dx.doi.org/10.1177/1352458521988926DOI Listing
February 2021

Oxidizing Cerium(IV) Alkoxide Complexes Supported by the Kläui Ligand [Co(η-CH){P(O)(OEt)}]: Synthesis, Structure, and Redox Reactivity.

Inorg Chem 2021 Feb 27;60(4):2261-2270. Epub 2021 Jan 27.

Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, P. R. China.

Tetravalent cerium alkoxide complexes supported by the Kläui tripodal ligand [Co(η-CH){P(O)(OEt)}] (L) have been synthesized, and their nucleophilic and redox reactivity have been studied. Treatment of the Ce(IV) oxo complex [Ce(L)(O)(HO)]·MeCONH () with PrOH or reaction of [Ce(L)Cl] () with AgO in PrOH afforded the Ce(IV) dialkoxide complex [Ce(L)(OPr)] (). The methoxide and ethoxide analogues [Ce(L)(OR)] (R = Me (), Et ()) have been prepared similarly from and AgO in ROH. Reaction of with an equimolar amount of yielded a new Ce(IV) complex that was formulated as the chloro-alkoxide complex [Ce(L)(OPr)Cl] (). Treatment of with HX and methyl triflate (MeOTf) afforded [Ce(L)X] (X = Cl, NO, PhO) and [Ce(L)(OTf)], respectively, whereas treatment with excess CO in hexane led to isolation of the Ce(IV) carbonate [Ce(L)(CO)]. reacted with water in hexane to give a Ce(III) complex and a Ce(IV) species, presumably the reported tetranuclear oxo cluster [Ce(L)(O)(OH)]. The Ce(IV) alkoxide complexes are capable of oxidizing substituted phenols, possibly via a proton-coupled electron transfer pathway. Treatment of with ArOH afforded the Ce(III) aryloxide complexes [Ce(L)(OAr)] (Ar = 2,4,6-tri--butylphenyl (), 2,6-diphenylphenyl ()). On the other hand, a Ce(III) complex containing a monodeprotonated 2,2'-biphenol ligand, [Ce(L)(BuCHOH)] () (BuCHOH = 4,4',6,6'-tetra--butyl-2,2'-biphenol), was isolated from the reaction of with 2,4-di--butylphenol. The crystal structures of complexes , , , and - have been determined.
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http://dx.doi.org/10.1021/acs.inorgchem.0c03105DOI Listing
February 2021

Heightened resistance to host type 1 interferons characterizes HIV-1 at transmission and after antiretroviral therapy interruption.

Sci Transl Med 2021 01;13(576)

Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA.

Type 1 interferons (IFN-I) are potent innate antiviral effectors that constrain HIV-1 transmission. However, harnessing these cytokines for HIV-1 cure strategies has been hampered by an incomplete understanding of their antiviral activities at later stages of infection. Here, we characterized the IFN-I sensitivity of 500 clonally derived HIV-1 isolates from the plasma and CD4 T cells of 26 individuals sampled longitudinally after transmission or after antiretroviral therapy (ART) and analytical treatment interruption. We determined the concentration of IFNα2 and IFNβ that reduced viral replication in vitro by 50% (IC) and found consistent changes in the sensitivity of HIV-1 to IFN-I inhibition both across individuals and over time. Resistance of HIV-1 isolates to IFN-I was uniformly high during acute infection, decreased in all individuals in the first year after infection, was reacquired concomitant with CD4 T cell loss, and remained elevated in individuals with accelerated disease. HIV-1 isolates obtained by viral outgrowth during suppressive ART were relatively IFN-I sensitive, resembling viruses circulating just before ART initiation. However, viruses that rebounded after treatment interruption displayed the highest degree of IFNα2 and IFNβ resistance observed at any time during the infection course. These findings indicate a dynamic interplay between host innate responses and the evolving HIV-1 quasispecies, with the relative contribution of IFN-I to HIV-1 control affected by both ART and analytical treatment interruption. Although elevated at transmission, host innate pressures are the highest during viral rebound, limiting the viruses that successfully become reactivated from latency to those that are IFN-I resistant.
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http://dx.doi.org/10.1126/scitranslmed.abd8179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923595PMC
January 2021

Dynamics of Transforming Growth Factor (TGF)-β Superfamily Cytokine Induction During HIV-1 Infection Are Distinct From Other Innate Cytokines.

Front Immunol 2020 24;11:596841. Epub 2020 Nov 24.

Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.

Human immunodeficiency virus type 1 (HIV-1) infection triggers rapid induction of multiple innate cytokines including type I interferons, which play important roles in viral control and disease pathogenesis. The transforming growth factor (TGF)-β superfamily is a pleiotropic innate cytokine family, some members of which (activins and bone morphogenetic proteins (BMPs)) were recently demonstrated to exert antiviral activity against Zika and hepatitis B and C viruses but are poorly studied in HIV-1 infection. Here, we show that TGF-β is systemically induced with very rapid kinetics (as early as 1-4 days after viremic spread begins) in acute HIV-1 infection, likely due to release from platelets, and remains upregulated throughout infection. Contrastingly, no substantial systemic upregulation of activins A and B or BMP-2 was observed during acute infection, although plasma activin levels trended to be elevated during chronic infection. HIV-1 triggered production of type I interferons but not TGF-β superfamily cytokines from plasmacytoid dendritic cells (DCs) , putatively explaining their differing induction; whilst lipopolysaccharide (but not HIV-1) elicited activin A production from myeloid DCs. These findings underscore the need for better definition of the protective and pathogenic capacity of TGF-β superfamily cytokines, to enable appropriate modulation for therapeutic purposes.
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http://dx.doi.org/10.3389/fimmu.2020.596841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732468PMC
June 2021

Global E-waste management: Can WEEE make a difference? A review of e-waste trends, legislation, contemporary issues and future challenges.

Waste Manag 2021 Feb 9;120:549-563. Epub 2020 Dec 9.

School of Geography and Environmental Science, Faculty of Environmental and Life Sciences, University of Southampton, Highfield Campus, Southampton SO17 1BJ, United Kingdom.

Waste electrical and electronic equipment (WEEE) comprises a globally important waste stream due to the scarcity and value of the materials that it contains; annual generation of WEEE is increasing by 3-5% per annum. The effective management of WEEE will contribute critically to progress towards (1) realisation of the United Nations' Sustainable Development Goals, (2) a circular economy, and (3) resource efficiency. This comprehensive review paper provides a critical and contemporary examination of the current global situation of WEEE management and discusses opportunities for enhancement. Trends in WEEE generation, WEEE-related policies and legislation are exemplified in detail. Four typical future WEEE management scenarios are identified, classified and outlined. The European Community is at the forefront of WEEE management, largely due to the WEEE Directive (Directive 2012/19/EU) which sets high collection and recycling targets for Member States. WEEE generation rates are increasing in Africa though collection and recycling rates are low. WEEE-related legislation coverage is increasing in Asia (notably China and India) and in Latin America. This review highlights emerging concerns, including: stockpiling of WEEE devices; reuse standards; device obsolescence; the Internet of Things, the potential for collecting space e-debris, and emerging trends in electrical and electronic consumer goods. Key areas of concern in regard to WEEE management are identified: the partial provision of formal systems for WEEE collection and treatment at global scale; further escalation of global WEEE generation (increased ownership, and acceleration of obsolescence and redundancy); and absence of regulation and its enforcement. Measures to improve WEEE management at global scale are recommended: incorporation of circular economy principles in EEE design and production, and WEEE management, including urban mining; extension of WEEE legislation and regulation, and improved enforcement thereof; harmonisation of key terms and definitions to permit consistency and meaning in WEEE management; and improvements to regulation and recognition of the informal WEEE management sector.
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http://dx.doi.org/10.1016/j.wasman.2020.10.016DOI Listing
February 2021

Robust Supramolecular Nano-Tunnels Built from Molecular Bricks*.

Angew Chem Int Ed Engl 2021 Mar 9;60(13):7148-7154. Epub 2021 Feb 9.

Department of Chemistry, The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, SCUT-HKUST Joint Research Institute, Institute for Advanced Study, Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.

Herein we report a linear ionic molecule that assembles into a supramolecular nano-tunnel structure through synergy of trident-type ionic interactions and π-π stacking interactions. The nano-tunnel crystal exhibits anisotropic guest adsorption behavior. The material shows good thermal stability and undergoes multi-stage single-crystal-to-single-crystal phase transformations to a nonporous structure on heating. The material exhibits a remarkable chemical stability under both acidic and basic conditions, which is rarely observed in supramolecular organic frameworks and is often related to structures with designed hydrogen-bonding interactions. Because of the high polarity of the tunnels, this molecular crystal also shows a large CO -adsorption capacity while excluding other gases at ambient temperature, leading to high CO /CH selectivity. Aggregation-induced emission of the molecules gives the bulk crystals vapochromic properties.
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http://dx.doi.org/10.1002/anie.202013117DOI Listing
March 2021

Albofungin and chloroalbofungin: antibiotic crystals with 2D but not 3D isostructurality.

Acta Crystallogr C Struct Chem 2020 12 25;76(Pt 12):1100-1107. Epub 2020 Nov 25.

Hong Kong Branch of the Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, People's Republic of China.

The potent antibiotics albofungin [systematic name: (1S,4R,8aR)-13-amino-1,15,16-trihydroxy-4-methoxy-12-methyl-3,4,8a,13-tetrahydro-1H-xantheno[4',3',2':4,5][1,3]benzodioxino[7,6-g]isoquinoline-14,17(2H,9H)-dione, CHNO, 1] and its chlorinated analogue chloroalbofungin (the 11-chloro analogue, CHClNO, 2) have been crystallized following their isolation from the bacterial strain Streptomyces chrestomyceticus and their structures determined by single-crystal X-ray diffraction. The novel N-aminoquinolone molecular arrangement shows N-N bond lengths of 1.4202 (16) and 1.424 (2) Å in 1 and 2, respectively. The regiochemistry of chloro substitution in the A-ring is para to the quinolone O atom, with a C-Cl bond length of 1.741 (2) Å. The absolute stereochemistry at three chiral centres of the xanthone rings (i.e. 10S, 13R and 19R) is confirmed. Both compounds crystallize in chiral Sohncke space groups consistent with enantiopurity, but are not fully isostructural. A preserved supramolecular construct (SC) confers two-dimensional (2D) isostructurality, but the SC self-associates via either a twofold screw operation in 1, giving a monoclinic P2 structure, or a twofold rotation in 2, affording a monoclinic C2 structure with a doubled unit-cell axis.
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http://dx.doi.org/10.1107/S2053229620015041DOI Listing
December 2020

Diffusioosmotic and convective flows induced by a nonelectrolyte concentration gradient.

Proc Natl Acad Sci U S A 2020 10 28;117(41):25263-25271. Epub 2020 Sep 28.

Institute for Bioengineering of Catalonia, The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain.

Glucose is an important energy source in our bodies, and its consumption results in gradients over length scales ranging from the subcellular to entire organs. Concentration gradients can drive material transport through both diffusioosmosis and convection. Convection arises because concentration gradients are mass density gradients. Diffusioosmosis is fluid flow induced by the interaction between a solute and a solid surface. A concentration gradient parallel to a surface creates an osmotic pressure gradient near the surface, resulting in flow. Diffusioosmosis is well understood for electrolyte solutes, but is more poorly characterized for nonelectrolytes such as glucose. We measure fluid flow in glucose gradients formed in a millimeter-long thin channel and find that increasing the gradient causes a crossover from diffusioosmosis-dominated to convection-dominated flow. We cannot explain this with established theories of these phenomena which predict that both scale linearly. In our system, the convection speed is linear in the gradient, but the diffusioosmotic speed has a much weaker concentration dependence and is large even for dilute solutions. We develop existing models and show that a strong surface-solute interaction, a heterogeneous surface, and accounting for a concentration-dependent solution viscosity can explain our data. This demonstrates how sensitive nonelectrolyte diffusioosmosis is to surface and solution properties and to surface-solute interactions. A comprehensive understanding of this sensitivity is required to understand transport in biological systems on length scales from micrometers to millimeters where surfaces are invariably complex and heterogeneous.
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http://dx.doi.org/10.1073/pnas.2009072117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568292PMC
October 2020

Lessons Learned from a Decade of Investigations of Shiga Toxin-Producing Escherichia coli Outbreaks Linked to Leafy Greens, United States and Canada.

Emerg Infect Dis 2020 10;26(10):2319-2328

Shiga toxin-producing Escherichia coli (STEC) cause substantial and costly illnesses. Leafy greens are the second most common source of foodborne STEC O157 outbreaks. We examined STEC outbreaks linked to leafy greens during 2009-2018 in the United States and Canada. We identified 40 outbreaks, 1,212 illnesses, 77 cases of hemolytic uremic syndrome, and 8 deaths. More outbreaks were linked to romaine lettuce (54%) than to any other type of leafy green. More outbreaks occurred in the fall (45%) and spring (28%) than in other seasons. Barriers in epidemiologic and traceback investigations complicated identification of the ultimate outbreak source. Research on the seasonality of leafy green outbreaks and vulnerability to STEC contamination and bacterial survival dynamics by leafy green type are warranted. Improvements in traceability of leafy greens are also needed. Federal and state health partners, researchers, the leafy green industry, and retailers can work together on interventions to reduce STEC contamination.
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http://dx.doi.org/10.3201/eid2610.191418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510726PMC
October 2020

Single-Cell RNA Sequencing Unveils Unique Transcriptomic Signatures of Organ-Specific Endothelial Cells.

Circulation 2020 Nov 15;142(19):1848-1862. Epub 2020 Sep 15.

Stanford Cardiovascular Institute (D.T.P., L.T., I.M.W., H.Z., C.L., R.M., S.M.W., K.R.-H., J.C.W.), Stanford University, CA.

Background: Endothelial cells (ECs) display considerable functional heterogeneity depending on the vessel and tissue in which they are located. Whereas these functional differences are presumably imprinted in the transcriptome, the pathways and networks that sustain EC heterogeneity have not been fully delineated.

Methods: To investigate the transcriptomic basis of EC specificity, we analyzed single-cell RNA sequencing data from tissue-specific mouse ECs generated by the Tabula Muris consortium. We used a number of bioinformatics tools to uncover markers and sources of EC heterogeneity from single-cell RNA sequencing data.

Results: We found a strong correlation between tissue-specific EC transcriptomic measurements generated by either single-cell RNA sequencing or bulk RNA sequencing, thus validating the approach. Using a graph-based clustering algorithm, we found that certain tissue-specific ECs cluster strongly by tissue (eg, liver, brain), whereas others (ie, adipose, heart) have considerable transcriptomic overlap with ECs from other tissues. We identified novel markers of tissue-specific ECs and signaling pathways that may be involved in maintaining their identity. Sex was a considerable source of heterogeneity in the endothelial transcriptome and we discovered to be a gene that is highly enriched in ECs from male mice. We found that markers of heart and lung ECs in mice were conserved in human fetal heart and lung ECs. We identified potential angiocrine interactions between tissue-specific ECs and other cell types by analyzing ligand and receptor expression patterns.

Conclusions: We used single-cell RNA sequencing data generated by the consortium to uncover transcriptional networks that maintain tissue-specific EC identity and to identify novel angiocrine and functional relationships between tissue-specific ECs.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.041433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658053PMC
November 2020
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