Precision Medicine Approaches to Vascular Disease: JACC Focus Seminar 2/5

In this second of a 5-part Focus Seminar series, we focus on precision medicine in the context of vascular disease. The most common vascular disease worldwide is atherosclerosis, which is the primary cause of coronary artery disease, peripheral vascular disease, and a large proportion of strokes and other disorders. Atherosclerosis is a complex genetic disease that likely involves many hundreds to thousands of single nucleotide polymorphisms, each with a relatively modest effect for causing disease. Conversely, although less prevalent, there are many vascular disorders that typically involve only a single genetic change, but these changes can often have a profound effect that is sufficient to cause disease. These are termed “Mendelian vascular diseases,” which include Marfan and Loeys-Dietz syndromes. Given the very different genetic basis of atherosclerosis versus Mendelian vascular diseases, this article was divided into 2 parts to cover the most promising precision medicine approaches for these disease types.     

Relationship between human leukocyte antigen-DRB1 and autoimmune hepatitis type I in Chinese patients

AIM: To analyze the association of human leukocyte antigen (HLA)-DRB1 with autoimmune hepatitis type I (AIH) among Chinese patients in the Shanghai area. METHODS: In 32 patients and 48 healthy controls, polymerase chain reaction amplified with sequence-specific primers (PCR-SSP) was performed to elucidate the relevance of certain alleles or polymorphic sequences of HLA-DRB1 with autoimmune hepatitis. RESULTS: The HLA-DRB1 typing by PCR-SSP showed that DR4 had a significantly increased frequency among patients with AIH versus that of healthy controls (46.9 vs 20.8%; relative risk = 3.35, P = 0.014). In the subtypes of DR4, there was a trend of an increase in the gene frequency of DRB1*0405 in patients with AIH versus that of healthy controls (21.9 vs 6.3%, P = 0.04, but corrected P (Pc) = 0.08). In addition, our analysis indicated a significant increase in the alleles frequency encoding Leu-Leu-Glu-Gln-Lys-Arg (LLEQRR) from the third hyperpolymorphic region (HVR3) of DR4 in the patients with AIH (86.7% of DR4 positive patients vs 40.0% in DR4 positive controls, P = 0.016, Pc = 0.028, relative risk (RR) = 9.75). CONCLUSION: Type I AIH among Chinese patients is associated with HLA-DR4. There is a relevance of type I AIH and LLEQRR sequence within the third hyperpolymorphic region of the DRB1 allele.     

Sealing of anodized magnesium alloy AZ31 with MgAl layered double hydroxides layers

In this work, anodized magnesium alloy AZ31 with and without boiling water sealing was pre-prepared, and then MgAl-layered double hydroxide (LDH) films were fabricated on it through hydrothermal chemical conversion of the pre-prepared anodic layer. The morphology, structure, and composition of the films were characterized by XRD, SEM, EDS, FT-IR, XPS and GDOES. It was found that the porosity of the films was reduced after in situ fabrication of the LDHs. The effects of boiling water sealing treatment on the anodized substrate were also discussed. Moreover, the polarization curve, EIS, and immersion tests showed that LDHs fabricated on the anodized substrate with boiling water sealing treatment exhibited a significant long period of protection for the substrate.

In this work anodized magnesium alloy AZ31 with and without boiling water sealing was pre-prepared, and then MgAl-layered double hydroxide (LDH) films were fabricated on it through hydrothermal chemical conversion of the pre-prepared anodic layer.     

Corrosion behavior of 904L austenitic stainless steel in hydrofluoric acid

Corrosion behaviors of 904L austenitic stainless steel in HF and HCl were studied and compared using electrochemical method, microscopic analysis, and phase analysis. An insoluble layer is deposited on 904L in HF due to a preferential reaction between [F⁻] and the [Ni] from the alloy. This insoluble deposited layer not only helps isolate the aggressive ions from the base metal, but also inhibits the passivation of 904L in HF, the mechanism for which was entirely different from that in HCl.

An insoluble layer is deposited on 904L in HF due to a preferential reaction between [F⁻] and the [Ni] from the alloy. This insoluble deposit layer helps isolate the aggressive ions from the base metal, while inhibits the passivation of 904L in HF.     

A carbonised sieve-like corn straw cellulose–graphene oxide composite for organophosphorus pesticide removal

The development of efficient adsorbents for the removal of organophosphorus pesticides from water is a major challenge. In this work, we prepared an activated carbon derived from sieve-like cellulose/graphene oxide composites (ACCE/G) for the removal of several organophosphorus pesticides. We employed corn straw to produce a sieve-like cellulose–graphene oxide composite (CCE/G); then, by treating CCE/G with potassium hydroxide at high temperatures, the efficient adsorbent ACCE/G was prepared. The adsorption capacity of ACCE/G is higher than those of other sorbents, including a multi-wall carbon nanotube, graphitised carbon black, activated carbon, C18, and primary secondary amine adsorbent. The ACCE/G structure has been fully characterised via scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction and Brunauer–Emmett–Teller analysis. The maximum adsorption capacity of ACCE/G is 152.5 mg g⁻¹ for chlorpyrifos. The mechanism, the thermodynamic properties, and the kinetics of the adsorption process have been investigated as well. Our findings demonstrate that the adsorption mechanism depends on the electron-donating abilities of the S and P atoms. Moreover, the Langmuir model gives the best fit for the isotherm data, and the adsorption efficiency of the ACCE/G is still over 80% after eight times of recycling, making ACCE/G a valuable candidate for the removal of OPPs.

Synthesizing a reusable adsorbent from waste corn straw is a sustainable way to utilize secondary resources and purify water.     

Correction: Synthesis,and single crystal structure of fully-substituted polynitrobenzene derivatives for high-energy materials

Correction for ‘Synthesis, and single crystal structure of fully-substituted polynitrobenzene derivatives for high-energy materials’ by Wei Yang et al., RSC Adv., 2018, 8, 2203–2208.

The literature citation to molecule 1 in Scheme 1 was in error and should have been to ref. 8; the corrected Scheme 1 is attached.Open in a separate windowScheme 1Synthetic strategy of polynitrobenzene derivatives for energetic materials.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Variability of native T1 values: implication for defining regional myocardial changes using MRI

The aim of the present study was to establish T1 variation (T1v) thresholds for duplicated measurements of regional T1 values in left ventricle (LV) using magnetic resonance imaging (MRI). Eighteen healthy volunteers were recruited to undergo two consecutive cardiac MRI scans using modified Look-Locker Inversion recovery (MOLLI) with two spatial resolutions on different days to repeat T1 measurements on LV. The absolute differences (d) and standard deviations (SDs) of regional T1 values were acquired with the two scans and two readers. T1v threshold (mean difference?+?2SD), intra-class correlation coefficient (ICC) and coefficient of variation (CoV) were calculated. T1 mapping using the MOLLI sequence (with multiple spatial resolutions) was successfully performed in all 18 volunteers twice. On a per-slice basis, ICCs for intra-observer, inter-observer, inter-resolution and inter-study T1v were 0.988, 0.899, 0.763 and 0.6. CoVs were 0.72, 2.39, 3.90 and 4.28%. T1v thresholds were 22, 66, 118 and 120 ms. On a per-segment basis, ICCs for intra-observer, inter-observer, inter-resolution and inter-study T1v were 0.974, 0.859, 0.711 and 0.594. CoVs were 1.09, 3.36, 4.69 and 5.01%. T1v thresholds were 33, 94, 140 and 144 ms. Those thresholds may be useful for discriminating disease-initiated T1v from random errors of T1 measurements.     

Research advances on the mechanism of biofilm formation in Acinetobacter baumannii北大核心CSCD

[No abstract available]