Synthesis of Long-T1 Silicon Nanoparticles for Hyperpolarized 29Si Magnetic Resonance Imaging

We describe the synthesis, materials characterization and dynamic nuclear polarization (DNP) of amorphous and crystalline silicon nanoparticles for use as hyperpolarized magnetic resonance imaging (MRI) agents. The particles were synthesized by means of a metathesis reaction between sodium silicide (Na4Si4) and silicon tetrachloride (SiCl4) and were surface functionalized with a variety of passivating ligands. The synthesis scheme results in particles of diameter ~10 nm with long size-adjusted 29Si spin lattice relaxation (T1) times (> 600 s), which are retained after hyperpolarization by low temperature DNP.Comment: Supporting material: https://dl.dropboxusercontent.com/u/1742676/Supporting_Atkins_v11.pd

Supplementary material for the article: Gruden, M.; Andjelkovic, L.; Jissy, A. K.; Stepanović, S.; Zlatar, M.; Cui, Q.; Elstner, M. Benchmarking Density Functional Tight Binding Models for Barrier Heights and Reaction Energetics of Organic Molecules. Journal of Computational Chemistry 2017, 38 (25), 2171–2185. https://doi.org/10.1002/jcc.24866

Supplementary material for:[https://doi.org/10.1002/jcc.24866]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2504

Use of statins for the prevention of cardiovascular disease in 41 low-income and middle-income countries: A cross-sectional study of nationally representative, individual-level data

BACKGROUND: In the prevention of cardiovascular disease, a WHO target is that at least 50% of eligible people use statins. Robust evidence is needed to monitor progress towards this target in low-income and middle-income countries (LMICs), where most cardiovascular disease deaths occur. The objectives of this study were to benchmark statin use in LMICs and to investigate country-level and individual-level characteristics associated with statin use. METHODS: We did a cross-sectional analysis of pooled, individual-level data from nationally representative health surveys done in 41 LMICs between 2013 and 2019. Our sample consisted of non-pregnant adults aged 40-69 years. We prioritised WHO Stepwise Approach to Surveillance (STEPS) surveys because these are WHO\u27s recommended method for population monitoring of non-communicable disease targets. For countries in which no STEPS survey was available, a systematic search was done to identify other surveys. We included surveys that were done in an LMIC as classified by the World Bank in the survey year; were done in 2013 or later; were nationally representative; had individual-level data available; and asked questions on statin use and previous history of cardiovascular disease. Primary outcomes were the proportion of eligible individuals self-reporting use of statins for the primary and secondary prevention of cardiovascular disease. Eligibility for statin therapy for primary prevention was defined among individuals with a history of diagnosed diabetes or a 10-year cardiovascular disease risk of at least 20%. Eligibility for statin therapy for secondary prevention was defined among individuals with a history of self-reported cardiovascular disease. At the country level, we estimated statin use by per-capita health spending, per-capita income, burden of cardiovascular diseases, and commitment to non-communicable disease policy. At the individual level, we used modified Poisson regression models to assess statin use alongside individual-level characteristics of age, sex, education, and rural versus urban residence. Countries were weighted in proportion to their population size in pooled analyses. FINDINGS: The final pooled sample included 116 449 non-pregnant individuals. 9229 individuals reported a previous history of cardiovascular disease (7·9% [95% CI 7·4-8·3] of the population-weighted sample). Among those without a previous history of cardiovascular disease, 8453 were eligible for a statin for primary prevention of cardiovascular disease (9·7% [95% CI 9·3-10·1] of the population-weighted sample). For primary prevention of cardiovascular disease, statin use was 8·0% (95% CI 6·9-9·3) and for secondary prevention statin use was 21·9% (20·0-24·0). The WHO target that at least 50% of eligible individuals receive statin therapy to prevent cardiovascular disease was achieved by no region or income group. Statin use was less common in countries with lower health spending. At the individual level, there was generally higher statin use among women (primary prevention only, risk ratio [RR] 1·83 [95% CI 1·22-2·76), and individuals who were older (primary prevention, 60-69 years, RR 1·86 [1·04-3·33]; secondary prevention, 50-59 years RR 1·71 [1·35-2·18]; and 60-69 years RR 2·09 [1·65-2·65]), more educated (primary prevention, RR 1·61 [1·09-2·37]; secondary prevention, RR 1·28 [0·97-1·69]), and lived in urban areas (secondary prevention only, RR 0·82 [0·66-1·00]). INTERPRETATION: In a diverse sample of LMICs, statins are used by about one in ten eligible people for the primary prevention of cardiovascular diseases and one in five eligible people for secondary prevention. There is an urgent need to scale up statin use in LMICs to achieve WHO targets. Policies and programmes that facilitate implementation of statins into primary health systems in these settings should be investigated for the future. FUNDING: National Clinician Scholars Program at the University of Michigan Institute for Healthcare Policy and Innovation, and National Institute of Diabetes and Digestive and Kidney Diseases. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section

Exploring the applicability of density functional tight binding to transition metal ions. Parameterization for nickel with the spin-polarized DFTB3 model

In this work, we explore the applicability and limitations of the current third order density functional tight binding (DFTB3) formalism for treating transition metal ions using nickel as an example. To be consistent with recent parameterization of DFTB3 for copper, the parametrization for nickel is conducted in a spin-polarized formulation and with orbital-resolved Hubbard parameters and their charge derivatives. The performance of the current parameter set is evaluated based on structural and energetic properties of a set of nickel-containing compounds that involve biologically relevant ligands. Qualitatively similar to findings in previous studies of copper complexes, the DFTB3 results are more reliable for nickel complexes with neutral ligands than for charged ligands; nevertheless, encouraging agreement is noted in comparison to the reference method, B3LYP/aug-cc-pVTZ, especially for structural properties, including cases that exhibit Jahn-Teller distortions; the structures also compare favorably to available X-ray data in the Cambridge Crystallographic Database for a number of nickel-containing compounds. As to limitations, we find it is necessary to use different d shell Hubbard charge derivatives for Ni(I) and Ni(II), due to the distinct electronic configurations for the nickel ion in the respective complexes, and substantial errors are observed for ligand binding energies, especially for charged ligands, d orbital splitting energies and splitting between singlet and triplet spin states for Ni(II) compounds. These observations highlight that future improvement in intra-d correlation and ligand polarization is required to enable the application of the DFTB3 model to complex transition metal ions.This project was supported by the Serbian-German collaboration project (DAAD) number 451-03-01038/2015-09/7 (to MG and ME), the Serbian Ministry of Science under project 172035 (to MG), NIH grant R01-GM106443 (QC) and the Spanish Ministry of Economy and Competitiveness through Grant FIS2015–64886-C5–2-P (P.G.-F.). P.G.-F. recognizes support from Ramón y Cajal Grant RyC-2013–12515

Real-Time MRI-Guided Catheter Tracking Using Hyperpolarized Silicon Particles

Visualizing the movement of angiocatheters during endovascular interventions is typically accomplished using x-ray fluoroscopy. There are many potential advantages to developing magnetic resonance imaging-based approaches that will allow three-dimensional imaging of the tissue/vasculature interface while monitoring other physiologically-relevant criteria, without exposing the patient or clinician team to ionizing radiation. Here we introduce a proof-of-concept development of a magnetic resonance imaging-guided catheter tracking method that utilizes hyperpolarized silicon particles. The increased signal of the silicon particles is generated via low-temperature, solid-state dynamic nuclear polarization, and the particles retain their enhanced signal for ≥40 minutes—allowing imaging experiments over extended time durations. The particles are affixed to the tip of standard medical-grade catheters and are used to track passage under set distal and temporal points in phantoms and live mouse models. With continued development, this method has the potential to supplement x-ray fluoroscopy and other MRI-guided catheter tracking methods as a zero-background, positive contrast agent that does not require ionizing radiation