Proteomic analysis reveals late exercise effects on cardiac remodeling following myocardial infarction

Exercise has been shown to improve function of the left ventricle (LV) following myocardial infarction (MI). The mechanisms to explain this benefit have not been fully delineated, but may involve improved mechanics resulting in unloading effects and increased endothelial nitric oxide synthase levels [1,2]. Accordingly, the goal of this study was to determine how the LV infarct proteome is altered by a post-MI exercise regimen. Sprague–Dawley rats underwent ligation of the left descending coronary artery to induce MI. Exercise training was initiated four weeks post-MI and continued for 8 weeks in n = 12 rats. Compared with the sedentary MI group (n = 10), the infarct region of rats receiving exercise showed 20 protein spots with altered intensities in two-dimensional gels (15 increased and 5 decreased; p < 0.05). Of 52 proteins identified in 20 spots, decreased levels of voltage-dependent anion-selective channel 2 and increased levels of glutathione perioxidase and manganese superoxide were confirmed by immunoblotting. Cardiac function was preserved in rats receiving exercise training, and the beneficial effect was linked with changes in these 3 proteins. In conclusion, our results suggest that post-MI exercise training increases anti-oxidant levels and decreases ion channel levels, which may explain, in part, the improved cardiac function seen with exercise.     

Detection of oesophageal course during left atrial catheter ablation

BackgroundOesophageal changes and injuries were recorded after atrial fibrillation(AF) ablation procedures. The reduction of power in the posterior left atrial(LA) wall(closest to the oesophagus) and the monitoring of temperature in the oesophagus(OE) reduced oesophageal injuries. The intracardiac-echocardiography(ICE) with a Cartosound module provides two-dimensional imaging (2D) to assess detailed cardiac anatomy and its relationship with the OE. The aim of this study was to highlight the safety and feasibility of 3D-reconstruction of the oesophageal course in left atrial catheter ablation(CA) procedures without OE temperature probe or quadripolar catheter to guide ICE OE reconstruction.Methods180 patients(PT) underwent left atrial ablation. AF ablation were 125(69.5%); incisional left atrial tachycardias(IAFL) were 37(20.6%); left atrial tachycardias(LAT) were 19(10.6%). The LA and pulmonary vein anatomies were rendered by traditional electroanatomic mapping(EAM) and merged with an ICE anatomic map. In 109 PT ICE imaging was used to create a geometry of the OE(group A). A quadripolar catheter was used in 71 PT to show OE course associated to ICE(group B).ResultsAblation energy delivery was performed outside the broadest OE anatomy borders. The duration of procedures was longer in group B vs group A Fluoroscopy time was lower in Group A than Group B(Group A 7 ± 3.2 vs 19.2 ± 2.4 min; p < 0.01).ConclusionsOE monitoring with ICE is safe and feasible. Oesophageal anatomy is complex and variable. Many PT will have a broad oesophageal boundary, which increases the risk of untoward thermal injury during posterior LA ablation. ICE with 3D construction of the OE enhances border detection of the OE, and as such, should decrease the risk of oesophageal injury by improving avoidance strategies without intra-oesophageal catheter visualization.     

Persistent left superior caval vein draining into right atrium,but not through the coronary sinus

Persistence of the left superior caval vein is the most commonly reported thoracic venous anomaly. The vein usually drains into the right atrium through the coronary sinus, reflecting its developmental origin. We describe an unusual variant, in which the vein drained directly into the right atrium.     

Skin dose in radiation treatment of the left breast: Analysis in the context of prone versus supine treatment technique

PurposeTo determine how the skin dose varies in patients receiving radiation treatment for breast cancer in the prone and supine positions.MethodsFifty patients were scanned in the prone and supine positions. A radiation treatment plan was created for the left breast using a 6-MV beam for a prescribed dose of 42.66 Gy in 16 fractions. The dose was calculated using 1- and 2.5-mm calculation grid sizes and the surface dose was compared in both techniques.ResultsThe median gantry angles relative to the skin surface at the central axis were 8 and 52 degrees for treatment in the prone and supine positions, respectively. The mean dose difference between the prone and supine techniques was statistically significant from 3- to 5-mm depth for both grid sizes. For the 1-mm calculation grid size, the doses at 3-, 4-, and 5-mm depths in the prone and supine techniques were 87.80% and 89.10% (P < 0.003), 91.92% and 94.50% (P < 0.00), and 95.30% and 98.20% (P < 0.00), respectively; for the 2.5-mm grid size, the respective doses were 87.10% and 88.59% (P < 0.00), 91.60% and 94.63% (P < 0.00), and 95.10% and 97.80% (P < 0.00), respectively.ConclusionsThis study demonstrates that the prone technique facilitates a relatively lower skin dose than the supine technique. This observation is probably due to the beam angle. The beam is more perpendicular to the skin surface in the prone technique, whereas it is more tangential in the supine technique, which may deliver a higher skin dose. Thus, the dose to the skin should be evaluated in the prone technique, and if desired, the skin dose could be carefully augmented via a bolus or beam spoiler.     

Rhodopsin p.N78I dominant mutation causing sectorial retinitis pigmentosa in a pedigree with intrafamilial clinical heterogeneity

Objective

The purpose of this study was to determine the molecular basis of retinitis pigmentosa (RP) in a 4 affected sib-family segregating this retinal phenotype.

Methods

Affected sibs underwent complete ophthalmologic examination including funduscopic inspection, electroretinogram, fluorescein angiography, visual field measurement, and optical coherence tomography. Both parents were deceased after their sixties and were reported with no visual handicap. Molecular analysis included direct nucleotide sequencing of the rhodopsin gene (RHO), at chromosome 3q21–q24, in DNA from a total of 4 affected sibs. A total of 200 ethnically matched alleles were included as mutation controls.

Results

Sector RP was clinically documented in this family. Wide phenotypic variability was observed with visual acuities ranging from 20/20 to 20/200 and variable funduscopic appearance. Molecular analysis disclosed a c.233A>T mutation at RHO exon 1, predicting a missense p.N78I substitution.

Conclusions

Even though RP can be caused by mutations in a variety of genes, the RHO gene was chosen to be investigated in this RP family since it has been previously associated to sector disease. This case exemplifies the value of guiding RP molecular analysis based on funduscopic features.     

Methylenetetrahydrofolate reductase C677T mutation in patients with alopecia areata in Turkish population

Objective

Methylene-tetrahydrofolate reductase (MTHFR) is a key enzyme regulating folate metabolism and it is thought to influence DNA methylation and nucleic acid synthesis. Mutations in the MTHFR gene have been associated with several autoimmune disorders in previous studies. Alopecia areata (AA) is considered to be a tissue-specific autoimmune disease as the hair follicle has been targeted and antibodies to their own hair follicle structures have been developed. Since there is a common shared pathway between AA and other autoimmune disorders, we aimed to investigate a possible association between the MTHFR gene C677T mutation and AA susceptibility in the Turkish population.

Methods

The study included 136 patients affected by AA and 130 healthy controls. Genomic DNA was isolated and genotyped using a polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay for the MTHFR gene C677T mutation.

Results

The distributions of genotype and allele frequencies of MTHFR gene C677T mutation were statistically different between AA patients and the control group (p = 0.036 and p = 0.011, respectively). High differences were also observed when the patients and controls were compared according to CC versus CT + TT (p = 0.012). CT + TT genotypes and T allele of MTHFR gene C677T mutation were found to be a susceptibility factor for AA in the Turkish population.

Conclusion

The results suggest that MTHFR gene C677T mutation may have an effect on the risk of alopecia areata in the Turkish population. This is the first study reporting the association between the MTHFR (C677T) genotype and AA.     

14-3-3ε Gene variants in a Japanese patient with left ventricular noncompaction and hypoplasia of the corpus callosum

Background

Left ventricular noncompaction (LVNC) is a cardiomyopathy characterized by a prominent trabecular meshwork and deep intertrabecular recesses, and is thought to be due to an arrest of normal endomyocardial morphogenesis. However, the genes contributing to this process remain poorly understood. 14-3-3ε, encoded by YWHAE, is an adapter protein belonging to the 14-3-3 protein family which plays important roles in neuronal development and is involved in Miller–Dieker syndrome. We recently showed that mice lacking this gene develop LVNC. Therefore, we hypothesized that variants in YWHAE may contribute to the pathophysiology of LVNC in humans.

Methods and results

In 77 Japanese patients with LVNC, including the probands of 29 families, mutation analysis of YWHAE by direct DNA sequencing identified 7 novel variants. One of them, c.− 458G > T, in the YWHAE promoter, was identified in a familial patient with LVNC and hypoplasia of the corpus callosum. The − 458G > T variant is located within a regulatory CCAAT/enhancer binding protein (C/EBP) response element of the YWHAE promoter, and it reduced promoter activity by approximately 50%. Increased binding of an inhibitory C/EBPβ isoform was implicated in decreasing YWHAE promoter activity. Interestingly, we had previously shown that C/EBPβ is a key regulator of YWHAE.

Conclusions

These data suggest that the − 458G > T YWHAE variant contributes to the abnormal myocardial morphogenesis characteristic of LVNC as well as abnormal brain development, and implicate YWHAE as a novel candidate gene in pediatric cardiomyopathies.     

Proliferating cells in suborbital tissue drive eye migration in flatfish

The left/right asymmetry of adult flatfishes (Pleuronectiformes) is remarkable given the external body symmetry of the larval fish. The best-known change is the migration of their eyes: one eye migrates from one side to the other. Two extinct primitive pleuronectiformes with incomplete orbital migration have again attracted public attention to the mechanism of eye migration, a subject of speculation and research for over a century. Cranial asymmetry is currently believed to be responsible for eye migration. Contrary to that hypothesis, we show here that the initial migration of the eye is caused by cell proliferation in the suborbital tissue of the blind side and that the twist of frontal bone is dependent on eye migration. The inhibition of cell proliferation in the suborbital area of the blind side by microinjected colchicine was able to prevent eye migration and, thereafter, cranial asymmetry in juvenile Solea senegalensis (right sideness, Soleidae), Cynoglossus semilaevis (left sideness, Cynoglossidae), and Paralichthys olivaceus (left sideness, Paralichthyidae) with a bottom-dwelling lifestyle. Our results correct the current misunderstanding that eye migration is driven by the cranial asymmetry and simplify the explanation for broken left/right eye-symmetry. Our findings should help to focus the search on eye migration-related genes associated with cell proliferation. Finally, a novel model is proposed in this research which provides a reasonable explanation for differences in the migrating eye between, and sometimes within, different species of flatfish and which should aid in our overall understanding of eye migration in the ontogenesis and evolution of Pleuronectiformes.     

维持性血液透析患者腹主动脉钙化与左室重量指数、预后的关系及其影响因素分析

摘要 目的：研究维持性血液透析（MHD）患者腹主动脉钙化与左室重量指数（LVMI）、预后的关系及其影响因素。方法：将医院从2016年5月到2018年6月收治的182例MHD患者纳入研究。将所有患者按照腹主动脉钙化评分分为钙化组（腹主动脉钙化评分>0分）145例和非钙化组（腹主动脉钙化评分=0分）37例。分析比较两组LVMI、临床基线资料以及实验室检查指标水平的差异。采用多因素Logistic回归分析明确MHD患者腹主动脉钙化的影响因素。结果：钙化组LVMI明显高于非钙化组,差异有统计学意义（P＜0.05）。钙化组全因死亡率、心血管死亡率均高于非钙化组（P＜0.05）;且经Kaplan-Meier生存曲线分析发现：钙化组患者全因死亡累积生存率以及心血管死亡累积生存率均明显低于非钙化组（P＜0.05）。钙化组年龄、透析龄以及血磷、全段甲状旁腺激素水平均高于非钙化组,而25羟维生素D3水平低于非钙化组（P＜0.05）。经多因素Logistic回归分析发现：年龄、透析龄、血磷、全段甲状旁腺激素及LVMI均是MHD患者腹主动脉钙化的独立危险因素,而25羟维生素D3是MHD患者腹主动脉钙化的保护因素（P＜0.05）。结论：MHD患者腹主动脉钙化与LVMI、预后密切相关,且年龄、透析龄、以及血磷、全段甲状旁腺激素、25羟维生素D3、LVMI均是MHD患者腹主动脉钙化的影响因素。