Copy Number Deletion Has Little Impact on Gene Expression Levels in Racehorses

Copy number variations (CNVs), important genetic factors for study of human diseases, may have as large of an effect on phenotype as do single nucleotide polymorphisms. Indeed, it is widely accepted that CNVs are associated with differential disease susceptibility. However, the relationships between CNVs and gene expression have not been characterized in the horse. In this study, we investigated the effects of copy number deletion in the blood and muscle transcriptomes of Thoroughbred racing horses. We identified a total of 1,246 CNVs of deletion polymorphisms using DNA re-sequencing data from 18 Thoroughbred racing horses. To discover the tendencies between CNV status and gene expression levels, we extracted CNVs of four Thoroughbred racing horses of which RNA sequencing was available. We found that 252 pairs of CNVs and genes were associated in the four horse samples. We did not observe a clear and consistent relationship between the deletion status of CNVs and gene expression levels before and after exercise in blood and muscle. However, we found some pairs of CNVs and associated genes that indicated relationships with gene expression levels: a positive relationship with genes responsible for membrane structure or cytoskeleton and a negative relationship with genes involved in disease. This study will lead to conceptual advances in understanding the relationship between CNVs and global gene expression in the horse

Direct Observation of Defects and Increased Ion Permeability of a Membrane Induced by Structurally Disordered Cu/Zn-Superoxide Dismutase Aggregates

Interactions between protein aggregates and a cellular membrane have been strongly implicated in many protein conformational diseases. However, such interactions for the case of Cu/Zn superoxide dismutase (SOD1) protein, which is related to fatal neurodegenerative disorder amyotrophic lateral sclerosis (ALS), have not been explored yet. For the first time, we report the direct observation of defect formation and increased ion permeability of a membrane induced by SOD1 aggregates using a supported lipid bilayer and membrane patches of human embryonic kidney cells as model membranes. We observed that aggregated SOD1 significantly induced the formation of defects within lipid membranes and caused the perturbation of membrane permeability, based on surface plasmon resonance spectroscopy, atomic force microscopy and electrophysiology. In the case of apo SOD1 with an unfolded structure, we found that it bound to the lipid membrane surface and slightly perturbed membrane permeability, compared to other folded proteins (holo SOD1 and bovine serum albumin). The changes in membrane integrity and permeability were found to be strongly dependent on the type of proteins and the amount of aggregates present. We expect that the findings presented herein will advance our understanding of the pathway by which structurally disordered SOD1 aggregates exert toxicity in vivo

Core–Satellites Assembly of Silver Nanoparticles on a Single Gold Nanoparticle via Metal Ion-Mediated Complex

We report core–satellites (Au–Ag) coupled plasmonic nanoassemblies based on bottom-up, high-density assembly of molecular-scale silver nanoparticles on a single gold nanoparticle surface, and demonstrate direct observation and quantification of enhanced plasmon coupling (i.e., intensity amplification and apparent spectra shift) in a single particle level. We also explore metal ion sensing capability based on our coupled plasmonic core–satellites, which enabled at least 1000 times better detection limit as compared to that of a single plasmonic nanoparticle. Our results demonstrate and suggest substantial promise for the development of coupled plasmonic nanostructures for ultrasensitive detection of various biological and chemical analytes

On-Chip Colorimetric Detection of Cu²⁺ Ions via Density-Controlled Plasmonic Core–Satellites Nanoassembly

We report on an on-chip colorimetric method for the detection and analysis of Cu²⁺ ions via the targeted assembly of plasmonic silver nanoparticles (2.6 nm satellites) on density-controlled plasmonic gold nanoparticles (50 nm cores) on a glass substrate. Without any ligand modification of the nanoparticles, by directly using an intrinsic moiety (carboxylate ion, COO^–) surrounded with nanoparticles, the method showed a high selectivity for Cu²⁺, resulting in a nearly 2 times greater optical response compared to those of other metal ions via the targeted core–satellites assembly. By modulating the surface chemistry, it was possible to control the density of core gold nanoparticles on the surface, thus permitting easy tuning of the optical responses induced by plasmon coupling generated between each core–satellites nanostructure. Using chips with a controlled optimal core density, we observed the remarkable scattering color changes of the chips from green to yellow and finally to orange with the increase of Cu²⁺ concentration. The detection limits of the fabricated chips with controlled core densities (ca. 1821 and 3636 particles/100 μm²) are 10 nM and 10 pM, respectively, which are quite tunable and below the level of 20 μM (or 1.3 ppm) defined by the United States Environmental Protection Agency. The findings suggest that the method is a potentially promising protocol for detecting small molecules with target selectivity and the tunability of the detection limits by replacing with ligands and adjusting core densities

Non-culprit left main coronary artery disease in acute myocardial infarction complicated by cardiogenic shock.

ObjectivesWe evaluated the clinical impact of residual non-culprit left main coronary artery disease (LMCAD) on prognosis in patients undergoing emergent percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) complicated by cardiogenic shock (CS).MethodsA total of 429 patients who underwent PCI for AMI complicated by CS was enrolled from 12 centers in the Republic of Korea. The patients were divided into two groups according to presence of non-culprit LMCAD or not: the LMCAD non-culprit group (n = 43) and the no LMCAD group (n = 386). Primary outcome was major adverse cardiac event (MACE, defined as a composite of cardiac death, myocardial infarction, or repeat revascularization). Propensity score matching analysis was performed to reduce selection bias and potential confounding factors.ResultsDuring a 12-month follow-up, a total of 168 MACEs occurred (LMCAD non-culprit group, 17 [39.5%] vs. no LMCAD group, 151 [39.1%]). Multivariate analysis revealed no significant difference in the incidence of MACE at 12 months between the LMCAD non-culprit and no LMCAD groups (adjusted hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.58 to 1.62, p = 0.901). After propensity score matching, the incidence of MACE was still similar between the two groups (HR 0.64; 95% CI 0.33 to 1.23; p = 0.180). The similarity of MACEs between the two groups was consistent across a variety of subgroups.ConclusionsAfter adjusting for baseline differences, residual non-culprit LMCAD does not appear to increase the risk of MACEs at 12 months in patients undergoing emergent PCI for AMI complicated by CS

Waning Antibody Responses in Asymptomatic and Symptomatic SARS-CoV-2 Infection

We investigated the kinetics of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies in 7 asymptomatic persons and 11 patients with pneumonia. The geometric mean titer of neutralizing antibodies declined from 219.4 at 2 months to 143.7 at 5 months after infection, indicating a waning antibody response.Y

Changes in Anxiety Level and Personal Protective Equipment Use Among Healthcare Workers Exposed to COVID-19

Background: The relationship between changes in anxiety levels and personal protective equipment (PPE) use is yet to be evaluated. The present study assessed this relationship among healthcare workers (HCWs) involved in the care of patients with coronavirus disease 2019 (COVID-19). Methods: An online survey was conducted in a municipal hospital with 195 nationally designated negative pressure isolation units in Korea. Anxiety level was measured using the self-rating anxiety scale (SAS), and changes in anxiety levels were assessed based on the time when COVID-19 vaccine was introduced in March 2021 in Korea. Monthly PPE usage between June 2020 and May 2021 was investigated. Results: The mean SAS score (33.25 +/- 5.97) was within normal range and was lower than those reported in previous studies conducted before COVID-19 vaccination became available. Among the 93 HCWs who participated, 64 (68.8%) answered that their fear of contracting COVID-19 decreased after vaccination. The number of coveralls used per patient decreased from 33.6 to 0. However, a demand for more PPE than necessary was observed in situations where HCWs were exposed to body fluids and secretions (n = 38, 40.9%). Excessive demand for PPE was not related to age, working experience, or SAS score. Conclusion: Anxiety in HCWs exposed to COVID-19 was lower than it was during the early period of the pandemic, and the period before vaccination was introduced. The number of coveralls used per patient also decreased although an excessive demand for PPE was observed.N

Efficacy and safety of durable versus biodegradable polymer drug-eluting stents in patients with acute myocardial infarction complicated by cardiogenic shock

Abstract The clinical impact of different polymer technologies in newer-generation drug-eluting stents (DESs) for patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) remains poorly understood. We investigated the efficacy and safety of durable polymer DESs (DP-DESs) compared with biodegradable polymer DESs (BP-DESs). A total of 620 patients who underwent percutaneous coronary intervention with newer-generation DESs for AMI complicated by CS was divided into two groups based on polymer technology: the DP-DES group (n = 374) and the BP-DES group (n = 246). The primary outcome was target vessel failure (TVF) during a 12-month follow-up, defined as a composite of cardiac death, myocardial infarction, or target vessel revascularization. Both the DP-DES and BP-DES groups exhibited low stent thrombosis rates (1.3% vs. 1.6%, p = 0.660). The risk of TVF did not significantly differ between the two groups (34.2% vs. 28.5%, hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.69–1.29, p = 0.721). This finding remained consistent after adjustment with inverse probability of treatment weighting (28.1% vs. 25.1%, HR 0.98, 95% CI 0.77–1.27, p = 0.899). In AMI patients complicated by CS, the risk of a composite of cardiac death, myocardial infarction, or target vessel revascularization was not significantly different between those treated with DP-DESs and those treated with BP-DESs. Trial registration: RESCUE registry, https://clinicaltrials.gov/ct2/show/NCT02985008 , NCT02985008

SARS-CoV-2 shedding dynamics and transmission in immunosuppressed patients

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern have been emerging. However, knowledge of temporal and spatial dynamics of SARS-CoV-2 is limited. This study characterized SARS-CoV-2 evolution in immunosuppressed patients with long-term SARS-CoV-2 shedding for 73-250 days, without specific treatment. We conducted whole-genome sequencing of 27 serial samples, including 26 serial samples collected from various anatomic sites of two patients and the first positive sample from patient 2's mother. We analysed the intrahost temporal dynamics and genomic diversity of the viral population within different sample types. Intrahost variants emerging during infection showed diversity between individual hosts. Remarkably, N501Y, P681R, and E484K, key substitutions within spike protein, emerged in vivo during infection and became the dominant population. P681R, which had not yet been detected in the publicly available genome in Korea, appeared within patient 1 during infection. Mutually exclusive substitutions at residues R346 (R346S and R346I) and E484 (E484K and E484A) of spike protein and continuous turnover of these substitutions occurred. Unique genetic changes were observed in urine samples. A household transmission from patient 2 to his mother, at least 38 days after the diagnosis, was characterized. Viruses may differently mutate and adjust to the host selective pressure, which could enable the virus to replicate efficiently for fitness in each host. Intrahost variants could be candidate variants likely to spread to the population eventually. Our findings may provide new insights into the dynamics of SARS-CoV-2 in response to interactions between the virus and host.N