Echocardiographic Manifestations in Patients with Cardiac Sarcoidosis

BackgroundCardiac sarcoidosis is a life-threatening disease with protean clinical manifestations, including congestive heart failure (CHF), conduction disturbance, ventricular arrhythmia and sudden death. Nonetheless, it is difficult to diagnose cardiac sarcoidosis in the clinical setting. Some echocardiographic findings of cardiac sarcoidosis associated with other diagnostic tools (201thallium scintigraphy, 67gallium citrate scan, serum markers and others) may be helpful upon early suspicion and diagnosis of cardiac sarcoidosis.Materials and MethodsFifty-two patients (36 female) with cardiac sarcoidosis, with a mean age of 48 ± 14 years (range, 21–70 yr), underwent a series of echocardiographic follow-up (mean, 88 ± 48 mo) examinations, and important echocardiographic parameters and findings were recorded.ResultsThere were left ventricular (LV) regional wall motion abnormalities (RWMAs) noted in 40 (localized in 16, multiple in 24), dilatation of the LV with impaired LV contractility in 28, thinning of the basal interventricular septum (IVS) in 27, thinning of LV free wall in 18, apical aneurysm in 12, apical thrombus in two, mimicking hypertrophic cardiomyopathy (HCM) in two, pericardial effusion (PE) in two (with cardiac tamponade in one), and LV wall thinning and aneurysm formation after steroid therapy for cardiac sarcoidosis in two of 43 patients.ConclusionThinning of the basal IVS or LV free wall is a specific echocardiographic finding of cardiac sarcoidosis. Other echocardiographic findings of cardiac sarcoidosis may mimic coronary artery disease (LV RWMA or apical aneurysm), CHF, or HCM. PE and thinning of the LV wall after steroid therapy were also noted in rare situations

Long-term Clinical Outcomes Following Elective Stent Implantation for Unprotected Left Main Coronary Artery Disease

Background/PurposePercutaneous coronary intervention (PCI) has been increasingly adopted for unprotected left main coronary artery (LMCA) disease. The aim of this study was to evaluate the predictors of long-term clinical outcomes in patients after elective stent implantation for unprotected LMCA disease.MethodsA total of 122 patients with medically refractory angina who received coronary stenting for unprotected LMCA disease between August 1997 and December 2008 were included.ResultsDuring the follow-up period of 45 ± 35 months (range: 1–137 months), the incidence of repeated PCI and/or coronary artery bypass grafting (CABG), and cardiovascular and total mortality were 28% (34 patients), 20% (24 patients), and 25% (31 patients), respectively. Multivariate analysis revealed that young age [p = 0.02; hazard ratio (HR): 2.19, 95% confidence interval (CI): 1.11–4.30] and bare-metal stent (BMS) use (p = 0.02; HR: 5.35, 95% CI: 1.27–22.57) were the independent predictors of repeated PCI and/or CABG. Only lower left ventricular ejection fraction (LVEF) could predict both cardiovascular mortality (p = 0.003; HR: 4.25, 95% CI: 1.63–11.08) and total mortality (p = 0.002; HR: 3.95, 95% CI: 1.65–9.45). Lower LVEF (p = 0.001; HR: 0.31, 95% CI: 0.16–0.61) and small stent size (p = 0.01; HR: 5.95, 95% CI: 1.43–24.80) could predict the composite endpoint, including target vessel revascularization and total mortality.ConclusionWe showed that young age and BMS implantation could predict repeated PCI and/or CABG after stent implantation for unprotected LMCA disease. Only lower LVEF could predict both cardiovascular and total mortality. Lower LVEF and small stent size but not BMS implantation could predict composite target vessel revascularization/total mortality

Genomic heterogeneity of multiple synchronous lung cancer

Multiple synchronous lung cancers (MSLCs) present a clinical dilemma as to whether individual tumours represent intrapulmonary metastases or independent tumours. In this study we analyse genomic profiles of 15 lung adenocarcinomas and one regional lymph node metastasis from 6 patients with MSLC. All 15 lung tumours demonstrate distinct genomic profiles, suggesting all are independent primary tumours, which are consistent with comprehensive histopathological assessment in 5 of the 6 patients. Lung tumours of the same individuals are no more similar to each other than are lung adenocarcinomas of different patients from TCGA cohort matched for tumour size and smoking status. Several known cancer-associated genes have different mutations in different tumours from the same patients. These findings suggest that in the context of identical constitutional genetic background and environmental exposure, different lung cancers in the same individual may have distinct genomic profiles and can be driven by distinct molecular events

Structural and Functional Characterization of Mature Forms of Metalloprotease E495 from Arctic Sea-Ice Bacterium Pseudoalteromonas sp. SM495

E495 is the most abundant protease secreted by the Arctic sea-ice bacterium Pseudoalteromonas sp. SM495. As a thermolysin family metalloprotease, E495 was found to have multiple active forms in the culture of strain SM495. E495-M (containing only the catalytic domain) and E495-M-C1 (containing the catalytic domain and one PPC domain) were two stable mature forms, and E495-M-C1-C2 (containing the catalytic domain and two PPC domains) might be an intermediate. Compared to E495-M, E495-M-C1 had similar affinity and catalytic efficiency to oligopeptides, but higher affinity and catalytic efficiency to proteins. The PPC domains from E495 were expressed as GST-fused proteins. Both of the recombinant PPC domains were shown to have binding ability to proteins C-phycocyanin and casein, and domain PPC1 had higher affinity to C-phycocyanin than domain PPC2. These results indicated that the domain PPC1 in E495-M-C1 could be helpful in binding protein substrate, and therefore, improving the catalytic efficiency. Site-directed mutagenesis on the PPC domains showed that the conserved polar and aromatic residues, D26, D28, Y30, Y/W65, in the PPC domains played key roles in protein binding. Our study may shed light on the mechanism of organic nitrogen degradation in the Arctic sea ice

Brain-Targeted Proanthocyanidin Metabolites for Alzheimer's Disease Treatment

While polyphenolic compounds have many health benefits, the potential development of polyphenols for the prevention/treatment of neurological disorders is largely hindered by their complexity as well as limited knowledge regarding their bioavailability, metabolism and bioactivity, especially in the brain. We recently demonstrated that dietary supplementation with a specific grape-derived polyphenolic preparation (GP) significantly improves cognitive function in a mouse model of Alzheimer’s disease (AD). GP is comprised of the proanthocyanidin (PAC) catechin and epicatechin in monomeric (Mo), oligomeric, and polymeric (Po) forms. In this study we report that following oral administration of the independent GP forms, only Mo is able to improve cognitive function and only Mo metabolites can selectively reach and accumulate in the brain at a concentration of ~400 nM. Most importantly we report for the first time that a biosynthetic epicatechin metabolite, 3’-O-methyl-epicatechin-5-O-β-glucuronide (3’-O-Me-EC-Gluc), one of the PAC metabolites identified in the brain following Mo treatment, promotes basal synaptic transmission and long term potentiation at physiologically relevant concentrations in hippocampus slices through mechanisms associated with cAMP response element binding protein (CREB) signaling. Our studies suggest that select brain-targeted PAC metabolites benefit cognition by improving synaptic plasticity in the brain, and provide impetus to develop 3’-O-Me-EC-Gluc and other brain-targeted PAC metabolites to promote learning and memory in Alzheimer’s disease and other forms of dementia

Bioinformatic analyses of integral membrane transport proteins encoded within the genome of the planctomycetes species, Rhodopirellula baltica

Rhodopirellula baltica (R. baltica) is a Planctomycete, known to have intracellular membranes. Because of its unusual cell structure and ecological significance, we have conducted comprehensive analyses of its transmembrane transport proteins. The complete proteome of R. baltica was screened against the Transporter Classification Database (TCDB) to identify recognizable integral membrane transport proteins. 342 proteins were identified with a high degree of confidence, and these fell into several different classes. R. baltica encodes in its genome channels (12%), secondary carriers (33%), and primary active transport proteins (41%) in addition to classes represented in smaller numbers. Relative to most non-marine bacteria, R. baltica possesses a larger number of sodium-dependent symporters but fewer proton-dependent symporters, and it has dimethylsulfoxide (DMSO) and trimethyl-amine-oxide (TMAO) reductases, consistent with its Na-rich marine environment. R. baltica also possesses a Na-translocating NADH:quinone dehydrogenase (Na-NDH), a Na efflux decarboxylase, two Na-exporting ABC pumps, two Na-translocating F-type ATPases, two Na:H antiporters and two K:H antiporters. Flagellar motility probably depends on the sodium electrochemical gradient. Surprisingly, R. baltica also has a complete set of H-translocating electron transport complexes similar to those present in α-proteobacteria and eukaryotic mitochondria. The transport proteins identified proved to be typical of the bacterial domain with little or no indication of the presence of eukaryotic-type transporters. However, novel functionally uncharacterized multispanning membrane proteins were identified, some of which are found only in Rhodopirellula species, but others of which are widely distributed in bacteria. The analyses lead to predictions regarding the physiology, ecology and evolution of R. baltica

A compendium of genetic regulatory effects across pig tissues

The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model.</p