Rare Variants in GJA5 Are Associated With Early-Onset Lone Atrial Fibrillation

Background

Genetic factors are believed to be important in early-onset lone atrial fibrillation (AF). The gene GJA5 encodes the gap-junction protein Cx40, which together with Cx43 is responsible for the electrical coupling of the atrial cardiomyocytes. The regulatory single nucleotide polymorphism rs10465885 in GJA5 was recently associated with early-onset lone AF (< 60 years) and was also found to be strongly associated with Cx40 messenger RNA levels. We hypothesized that this gene would have a strong effect in patients with a more selected phenotype, and that the findings regarding rs10465885 could be replicated in this group.

Methods

The coding region and flanking intron sequences of GJA5 were resequenced in 342 patients with onset of lone AF before the age of 50 (mean age at onset 34 ± 9 years), and in 216 controls. The single nucleotide polymorphism rs10465885 was genotyped in 342 patients and 534 control subjects and odds ratios were calculated for different genetic models.

Results

Genotyping of rs10465885 showed that the patients with early-onset lone AF were more likely to carry the A allele compared with controls (odds ratio = 1.30; P = 0.011). When resequencing GJA5, we identified the mutation A96S, previously associated with lone AF, which was not present in our control subjects or in any publicly available database or the National Heart, Lung, and Blood Institute Exome Variant Server (NHLBI EVS; 10,758 alleles).

Conclusions

We show a highly significant association between the A allele of rs10465885 and onset of lone AF before age 50. This opposes a previous study, wherein the G allele was found to be associated with AF, and makes it impossible to exclude that the associations are coincidental.     

Genetic loci on chromosomes 4q25, 7p31, and 12p12 are associated with onset of lone atrial fibrillation before the age of 40 years

Background

Three distinct genetic loci on chromosomes 1q21, 4q25, and 16q22 have been associated with atrial fibrillation (AF) in genome-wide association studies (GWAS). Five additional loci have been associated primarily with the PR interval and subsequently with AF. We aimed to investigate if 8 single nucleotide polymorphisms (SNPs), representing the 8 genomic loci previously linked with AF in genome-wide association studies, were associated with early-onset lone AF.

Methods

We included 209 patients with early-onset lone AF, and a control group consisting of 534 individuals free of AF. The 8 SNPs were genotyped using TaqMan assays (Applied Biosystems, Foster City, CA).

Results

Three SNPs were found to be significantly associated with early-onset lone AF: rs2200733 closest to PITX2 (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.16-2.27; P = 0.004), rs3807989 near to CAV1 (OR 1.35; 95% CI, 1.06-1.72; P = 0.015), and rs11047543 near to SOX5 (OR 1.70; 95% CI, 1.18-2.44; P = 0.004). When correcting for multiple testing, rs2200733 and rs11047543 were still significantly associated with AF.

Conclusions

Three SNPs, rs2200733 (4q25), rs3807989 (7p31), and rs11047543 (12p12), were associated with early-onset lone AF. All 3 SNPs are positioned close to genes that in previous studies have been demonstrated to be important for cardiac morphology/development, thereby suggesting a link between these SNPs and structural heart disease. Our results however, indicate that variants in these 3 loci are associated with AF through mechanisms that do not involve major structural abnormalities in the heart.     

Development and Validation of a Metabolic-related Prognostic Model for Hepatocellular Carcinoma

Background and Aims: Growing evidence suggests that metabolic-related genes have a significant impact on the occurrence and development of hepatocellular carcin...     

Genome analysis of the smallest free-living eukaryote Ostreococcus tauri unveils many unique features

The green lineage is reportedly 1,500 million years old, evolving shortly after the endosymbiosis event that gave rise to early photosynthetic eukaryotes. In this study, we unveil the complete genome sequence of an ancient member of this lineage, the unicellular green alga Ostreococcus tauri (Prasinophyceae). This cosmopolitan marine primary producer is the world's smallest free-living eukaryote known to date. Features likely reflecting optimization of environmentally relevant pathways, including resource acquisition, unusual photosynthesis apparatus, and genes potentially involved in C(4) photosynthesis, were observed, as was downsizing of many gene families. Overall, the 12.56-Mb nuclear genome has an extremely high gene density, in part because of extensive reduction of intergenic regions and other forms of compaction such as gene fusion. However, the genome is structurally complex. It exhibits previously unobserved levels of heterogeneity for a eukaryote. Two chromosomes differ structurally from the other eighteen. Both have a significantly biased G+C content, and, remarkably, they contain the majority of transposable elements. Many chromosome 2 genes also have unique codon usage and splicing, but phylogenetic analysis and composition do not support alien gene origin. In contrast, most chromosome 19 genes show no similarity to green lineage genes and a large number of them are specialized in cell surface processes. Taken together, the complete genome sequence, unusual features, and downsized gene families, make O. tauri an ideal model system for research on eukaryotic genome evolution, including chromosome specialization and green lineage ancestry.     

Posttraumatic segmental axial dystonia.

Isolated dystonia of trunk and neck muscles without involvement elsewhere has been termed segmental axial dystonia--a rare disorder. We report a 31-year-old man who developed marked dystonia of paraspinal muscles and progressive scoliosis 6 months after a closed head injury. Computed tomography (CT) disclosed three small areas of encephalomalacia, one involving the head of the caudate nucleus. Treatment with trihexyphenidyl resulted in significant improvement of the dystonia and scoliosis.     

充气式牵引器在小儿肌性斜颈术后的应用

肌性斜颈术后早期应用充气式牵引器外固定能巩固手术疗效,减少术后病情复发。52例斜颈均得到矫正,头颈旋转角度改善,且简单、易操作、安全可靠。     

Galvanic coupling of steel and gold alloy lingual brackets with orthodontic wires: Is corrosion a concern?

Objectives:The aim of this research was to assess galvanic behavior of lingual orthodontic brackets coupled with representative types of orthodontic wires.Materials and Methods:Three types of lingual brackets: Incognito (INC), In-Ovation L (IOV), and STb (STB) were combined with a stainless steel (SS) and a nickel-titanium (NiTi) orthodontic archwire. All materials were initially investigated by scanning electron microscopy / x-ray energy dispersive spectroscopy (SEM/EDX) while wires were also tested by x-ray diffraction spectroscopy (XRD). All bracket-wire combinations were immersed in acidic 0.1M NaCl 0.1M lactic acid and neutral NaF 0.3% (wt) electrolyte, and the potential differences were continuously recorded for 48 hours.Results:The SEM/EDX analysis revealed that INC is a single-unit bracket made of a high gold (Au) alloy while IOV and STB are two-piece appliances in which the base and wing are made of SS alloys. The SS wire demonstrated austenite and martensite iron phase, while NiTi wire illustrated an intense austenite crystallographic structure with limited martensite. All bracket wire combinations showed potential differences below the threshold of galvanic corrosion (200 mV) except for INC and STB coupled with NiTi wire in NaF media.Conclusions:The electrochemical results indicate that all brackets tested demonstrated galvanic compatibility with SS wire, but fluoride treatment should be used cautiously with NiTi wires coupled with Au and SS brackets.     

One-step fabrication of nanosized LiFePO4/expanded graphite composites with a particle growth inhibitor and enhanced electrochemical performance of aqueous Li-ion capacitors

It is reported that olivine-type lithium iron phosphate (LFP) for Li-ion batteries is one of the most widely utilized cathode materials, but its high-power applications are limited due to its intrinsically poor ion transfer rate and conductivity. Therefore, it is highly desired to fabricate LFP Li-ion capacitors (LICs) with high power performance and excellent cyclic reversibility, especially in safe, low cost and environmentally friendly aqueous electrolytes. Here, we fabricate LFP/expanded graphite (EG) nanocomposites by a one-step process, in which polyethylene glycol (PEG) is used as the particle growth inhibitor combined with vacuum infiltration of the LFP precursor into EG as a conductive sub-phase, and further investigate their high-power performance in aqueous LICs. Embedding spherical LFP nanoparticles with well-controlled size and agglomeration into the pores of EG and wrapping LFP nanoparticles by EG films contribute to the rapid electron and ion diffusion in LFP/EG composites, resulting in excellent cyclic reversibility and rate performance of LFP/EG composites. The aqueous LFP/EG//active carbon (AC) LICs were assembled in LiNO₃ electrolytes with LFP/EG composites and AC as the positive and negative electrodes, respectively. The optimal LIC shows a power density of 2367.9 W kg⁻¹ at an energy density of 6.5 W h kg⁻¹, dramatically favorable rate characteristics and excellent cycle life with 82.1% capacitance retention of its primary capacitance at 2 A g⁻¹ after 6000 cycles, markedly higher than those of the commercial LFP LIC. The presented aqueous LFP/EG//AC LICs with excellent electrochemical performance are expected to have broad high-power appliances that are cost-sensitive and highly secure.

It is reported that olivine-type lithium iron phosphate (LFP) for Li-ion batteries is one of the most widely utilized cathode materials, but its high-power applications are limited due to its intrinsically poor ion transfer rate and conductivity.     

Inoperable esophageal cancer and outcome of palliative care

AIM： To determine the outcome of esophageal cancer patients referred for palliative care, in Gorgan and Gonbad gastrointestinal clinics, northeast of Iran.
METHODS： This cross-sectional study was done on inoperable esophageal cancer cases referred to gastrointestinal clinics in Gorgan and Gonbad city （2005-2006）. Demographic data were collected during the procedure and cases were followed up every one month. Improvement proportion was calculated with 95% confidence interval, to determine the rate of improvement. Survival analysis and Kaplan- Meier methods were used to estimate the duration of palliative care effectiveness.
RESULTS： We recruited 39 cases into the study. Squamous cell carcinoma was the most prevalent （92.3%）. The middle third of the esophagus was involved predominantly （51.3%）. Dilation was the most preferred method （89.7%） and stenting was done in 4 cases. Decreasing dysphagia score was not related to palliation method or pathology type of carcinoma. Age of the patients was significantly related to the improvement of dysphagia score. Mean survival time was 137.6 d and median was 103 d.
CONCLUSION： Results of this study showed a low survival rate after palliative care in esophageal cancer cases despite dysphagia scores＇ improvement after dilating or stenting.     

MOF-derived nitrogen-doped porous carbon nanofibers with interconnected channels for high-stability Li+/Na+ battery anodes

Heteroatom-doped porous carbon materials have been widely used as anode materials for Li-ion and Na-ion batteries, however, improving the specific capacity and long-term cycling stability of ion batteries remains a major challenge. Here, we report a facile based metal–organic framework (MOFs) strategy to synthesize nitrogen-doped porous carbon nanofibers (NCNFs) with a large number of interconnected channels that can increase the contact area between the material and the electrolyte, shorten the diffusion distance between Li⁺/Na⁺ and the electrolyte, and relieve the volume expansion of the electrode material during cycling; the doping of nitrogen atoms can improve the conductivity and increase the active sites of the carbon material, can also affect the microstructure and electron distribution of the electrode material, thereby improving the electrochemical performance of the material. As expected, the obtained NCNFs-800 exhibited excellent electrochemical performance with high reversible capacity (for Li⁺ battery anodes: 1237 mA h g⁻¹ at 100 mA g⁻¹ after 200 cycles, for Na⁺ battery anodes: 323 mA h g⁻¹ at 100 mA g⁻¹ after 150 cycles) and long-term cycling stability (for Li⁺ battery anodes: 635 mA h g⁻¹ at 2 A g⁻¹ after 5000 cycles, for Na⁺ battery anodes: 194 mA h g⁻¹ at 2 A g⁻¹ after 5000 cycles).

Heteroatom-doped porous carbon materials have been widely used as anode materials for Li-ion and Na-ion batteries, however, improving the specific capacity and long-term cycling stability of ion batteries remains a major challenge.