Prevalence and spectrum of Nkx2.5 mutations associated with idiopathic atrial fibrillation

OBJECTIVE: The aim of this study was to evaluate the prevalence and spectrum of Nkx2.5 mutations associated with idiopathic atrial fibrillation (AF). METHODS: A cohort of 136 unrelated patients with idiopathic atrial fibrillation and 200 unrelated, ethnically matched healthy controls were enrolled. The coding exons and splice junctions of the Nkx2.5 gene were sequenced in 136 atrial fibrillation patients, and the available relatives of mutation carriers and 200 controls were subsequently genotyped for the identified mutations. The functional characteristics of the mutated Nkx2.5 gene were analyzed using a dual-luciferase reporter assay system. RESULTS: Two novel heterozygous Nkx2.5 mutations (p.N19D and p.F186S) were identified in 2 of the 136 unrelated atrial fibrillation cases, with a mutational prevalence of approximately 1.47%. These missense mutations co-segregated with atrial fibrillation in the families and were absent in the 400 control chromosomes. Notably, 2 mutation carriers also had congenital atrial septal defects and atrioventricular block. Multiple alignments of the Nkx2.5 protein sequences across various species revealed that the altered amino acids were completely conserved evolutionarily. Functional analysis demonstrated that the mutant Nkx2.5 proteins were associated with significantly reduced transcriptional activity compared to their wild-type counterpart. CONCLUSION: These findings associate the Nkx2.5 loss-of-function mutation with atrial fibrillation and atrioventricular block and provide novel insights into the molecular mechanism involved in the pathogenesis of atrial fibrillation. These results also have potential implications for early prophylaxis and allele-specific therapy of this common arrhythmia

PITX2C loss-of-function mutations responsible for idiopathic atrial fibrillation

OBJECTIVE: This study aimed to identify novel PITX2c mutations responsible for idiopathic atrial fibrillation. METHODS: A cohort of 210 unrelated patients with idiopathic atrial fibrillation and 200 unrelated, ethnically matched healthy individuals used as controls were recruited. The whole coding exons and splice junctions of the PITX2c gene, which encodes a paired-like homeobox transcription factor required for normal cardiovascular morphogenesis, were sequenced in 210 patients and 200 control subjects. The causative potentials of the identified mutations were automatically predicted by MutationTaster and PolyPhen-2. The functional characteristics of the PITX2c mutations were explored using a dual-luciferase reporter assay system. RESULTS: Two novel heterozygous PITX2c mutations (p.Q105L and p.R122C) were identified in 2 of the 210 unrelated patients with idiopathic atrial fibrillation. These missense mutations were absent in the 400 control chromosomes and were both predicted to be pathogenic. Multiple alignments of PITX2c protein sequences across various species showed that the altered amino acids were highly evolutionarily conserved. A functional analysis demonstrated that the mutant PITX2c proteins were both associated with significantly reduced transcriptional activity compared with their wild-type counterparts. CONCLUSION: The findings of this study associate PITX2c loss-of-function mutations with atrial fibrillation, supporting the hypothesis that dysfunctional PITX2c confers enhanced susceptibility to atrial fibrillation and suggesting potential implications for early prophylaxis and allele-specific therapy for this common arrhythmia

The Large High Altitude Air Shower Observatory (LHAASO) Science White Paper

The Large High Altitude Air Shower Observatory (LHAASO) project is a new generation multi-component instrument, to be built at 4410 meters of altitude in the Sichuan province of China, with the aim to study with unprecedented sensitivity the spec trum, the composition and the anisotropy of cosmic rays in the energy range between 10$^{12}$ and 10$^{18}$ eV, as well as to act simultaneously as a wide aperture (one stereoradiant), continuously-operated gamma ray telescope in the energy range between 10$^{11}$ and $10^{15}$ eV. The experiment will be able of continuously surveying the TeV sky for steady and transient sources from 100 GeV to 1 PeV, t hus opening for the first time the 100-1000 TeV range to the direct observations of the high energy cosmic ray sources. In addition, the different observables (electronic, muonic and Cherenkov/fluorescence components) that will be measured in LHAASO will allow to investigate origin, acceleration and propagation of the radiation through a measurement of energy spec trum, elemental composition and anisotropy with unprecedented resolution. The remarkable sensitivity of LHAASO in cosmic rays physics and gamma astronomy would play a key-role in the comprehensive general program to explore the High Energy Universe. LHAASO will allow important studies of fundamental physics (such as indirect dark matter search, Lorentz invariance violation, quantum gravity) and solar and heliospheric physics. In this document we introduce the concept of LHAASO and the main science goals, providing an overview of the project.Comment: This document is a collaborative effort, 185 pages, 110 figure

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease

The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted as the document was compiled through December 2008. Repeated literature searches were performed by the guideline development staff and writing committee members as new issues were considered. New clinical trials published in peer-reviewed journals and articles through December 2011 were also reviewed and incorporated when relevant. Furthermore, because of the extended development time period for this guideline, peer review comments indicated that the sections focused on imaging technologies required additional updating, which occurred during 2011. Therefore, the evidence review for the imaging sections includes published literature through December 2011

Efficacy of adjunctive intravitreous injection with Lucentis for neovascular glaucoma

AIM: To observe the clinical efficacy of adjunctive intravitreous injection with Lucentis for the treatment of neovascular glaucoma(NVG). <p>METHODS: The retrospective case series study included 25 eyes of 25 patients who underwentintravitreous injection with Lucentis. Patients firstly received an intravitreous injection with Lucentis(0.5mg/0.05mL), after the regression of neovascularization of the iris, patients accepted different surgical treatments according to different etiopathogenesis condition. Iris, chamber angle neovascularization condition, intraocular pressure, and visual acuity were observed postoperatively. The follow-up duration was 3mo.<p>RESULTS: After 3-7d of intravitreous Lucentis injecting, iris and chamber angle neovascularization was totally faded in 20 cases(20 eyes)and was not completely faded in 5 cases(5 eyes). Additional treatments were compound trabeculectomy(14 cases, 14 eyes), vitrectomy(4 cases, 4 eyes). The patients' mean intraocular pressure was 43.42±10.99mmHg before treatment, which decreased rapidly when they came out of the hospital(14.26±7.64mmHg, <i>P</i><0.05)and stabilized during the follow-up 3mo(18.76±5.96mmHg, <i>P</i><0.05). Follow-up at 3mo, visual acuity improved or remained in 20 cases(20 eyes)and decreased in 5 cases(5 eyes). The complete success, qualified success and failure were 21 eyes, 3 eyes and 1 eye, respectively.<p>CONCLUSION:Intravitreous injection with Lucentis can be used as an assisted treatment of NVG. According to different etiopathogenesis condition, it is an effective treatment to combine with other treatment methods for NVG

Emotional working memory training reduces rumination and alters the EEG microstate in anxious individuals

Rumination is an important etiological factor of anxiety pathology, with its mechanism related to the deficit of working memory. The current study examined whether working memory training (WM-T) and emotional working memory training (EWM-T) could reduce rumination in anxious individuals. The participants with high trait anxiety underwent 21 days of mobile applications-based WM-T (n = 34), EWM-T (n = 36) or placebo control (n = 36), with questionnaires, cognitive tasks, and resting electroencephalogram (EEG) as the pre-post-test indicators. The results revealed that two training groups obtained comparable operation span increases (WM-T: d = 0.53; EWM-T: d = 0.65), updating improvement (WM-T: d = 0.43; EWM-T: d = 0.60) and shifting improvement (WM-T: d = 0.49; EWM-T: d = 0.72). Furthermore, compared to the control group, the EWM-T showed significant self-reported rumination reduction (d = 0.69), increased inhibition ability (d = 0.72), as well as modification of resting EEG microstate C parameters (Duration C: d = 0.42, Coverage C: d = 0.39), which were closely related to rumination level (r similar to 0.4). The WM-T group also showed the potential to reduced self-reported rumination (d = 0.45), but with the absence of the observable inhibition improvement and resting EEG changes. The correlation analysis suggested that the emotional benefits of WM-T depending more on improved updating and shifting, and that of EWM-T depending more on improved inhibition ability. The advantage to add emotional distractions into general working memory training for targeting rumination related anxiety has been discussed

Analysis of tear film and corneal endothelial cell density in cataract patients with high myopia

AIM: To observe the tear film and corneal endothelial cell density in cataract patients with high myopia.METHODS: From January 2016 to December 2016,38 cases(38 eyes)with high myopia and cataract were selected as study group, 24 males(24 eyes)and 14 females(14 eyes), average 65.2±2.37(60-72)years old. Age-related cataract patients without high myopia were as control group, 22 males(22 eyes)and 16 females(16 eyes), average 64.4±2.43(61-70)years old. The tear film and corneal endothelial cell density of the two groups were observed at 3, 7, 14d and 1mo after operations.RESULTS: Between the two groups of preoperative SⅠt, BUT, FL, subjective rating, corneal endothelial cell density comparison, there were no statistically significant difference(P>0.05). In the two groups at 3, 7, 14d and 1mo after operations, BUT, FL, corneal endothelial cell density, subjective score comparison, the difference had statistical significance(PPP>0.05). At postoperative 3, 7, 14d, 1mo, FL, subjective rating, corneal endothelial cell density of the two groups were compared with preoperative, the difference was statistically significant(PPP>0.05). BUT of high myopia patients with age-related cataract surgery, at 3, 7, 14d and 1mo after operations decreased than preoperative, the difference was statistically significant(PPP>0.05). CONCLUSION: Phacoemulsification cataract surgery in the treatment of high myopia cataract patients is safe and reliable, and less influence on tear film and corneal endothelial cell density