Clinical comparison and functional study of the L703P: a recurrent mutation in human SCN4A that causes sodium channel myotonia.

The non-dystrophic myotonias are inherited skeletal muscle disorders characterized by skeletal muscle stiffness after voluntary contraction, without muscle atrophy. Based on their clinical features, non-dystrophic myotonias are classified into myotonia congenita, paramyotonia congenita, and sodium channel myotonia. Using whole-exome next-generation sequencing, we identified a L703P mutation (c.2108T>C, p.L703P) in SCN4A in a Chinese family diagnosed with non-dystrophic myotonias. The clinical findings of patients in this family included muscle stiffness and hypertrophy. The biophysical properties of wildtype and mutant channels were investigated using whole-cell patch clamp. L703P causes both gain-of-function and loss-of-function changes in Nav1.4 properties, including decreased current density, impaired recovery, enhanced activation and slow inactivation. Our study demonstrates that L703P is a pathogenic variant for myotonia, and provides additional electrophysiological information for understanding the pathogenic mechanism of SCN4A-associated channelopathies.

One-step self-assembled synthesis of CuO with tunable hierarchical structures and their electrocatalytic properties for nitrite oxidation in aqueous media.

Controlled synthesis of CuO with various hierarchical structures consisting of self-organized nanoparticles is realized by using n-octylamine (OLA) as a structure inducing agent via a facile hydrothermal synthetic method. The growth and assemblage of CuO can be finely tuned by selecting the preparative parameters. In particular, it is found that the degree of the hierarchical organization can be modulated by simply changing the amount of the n-octylamine and CuO nanoparticles exhibit self-assembled two-dimensional (2D) sheet-like, three-dimensional (3D) disk-like and bowknot-like architectures, respectively. In the present case, OLA serves as a capping surfactant that can modulate growth of CuO nanocrystals via hydrophobic forces between the OLA molecules. CuO nanoparticles can be self-assembled into different complex architectures depending on the strength of hydrophobic forces. Hierarchical sphere-like CuO assembled from nanorods can also be easily fabricated by adjusting the starting NaOH to CuCl2 volume ratio, in which OLA serves not only as the structure-directing agent, but also as a weak base agent to produce hydroxyl anions. The electrochemical performances of the as-synthesized different products for sensing nitrite oxidation are evaluated. The results reveal that the electrocatalytic activity is related to the secondary nanostructures. Compared to the others, the bowknot-shaped and sphere-shaped CuO products exhibit excellent electrocatalytic activity toward nitrite oxidation and fast current response in nitrite sensing because of their peculiar hierarchical structures with high BET surface areas and well-ordered pores.

[A comparative study on the efficacy and safety of intravenous esmolol, amiodarone and diltiazem for controlling rapid ventricular rate of patients with atrial fibrillation during anesthesia period].

OBJECTIVE: To evaluate the efficacy and safety of intravenous esmolol, amiodarone and diltiazem for controlling rapid ventricular rate in patients with atrial fibrillation (AF) during anesthesia period. METHODS: Ninety AF patients with rapid atrial ventricular rate (≥ 120 beats/min) in anesthesia period were randomly divided into 3 groups (n = 30 each: group I patients were treated with intravenous esmolol (0.5 mg/kg loading dose within 1 minute followed with infusion of 0.05 mg×kg(-1)×min(-1)); group II patients were treated with intravenous amiodarone (loading dose: 3 mg/kg for 10 minutes, followed with intravenous infusion of 1 mg/min); group III patients were treated with intravenous diltiazem (0.25 mg/kg for 5 minutes). The heart rate, blood pressure, rhythm were recorded before treatment, at 5, 10, 15, 30, 60 and 90 min after treatment. The reacting time, side effects including hypotension, bradycardia, nausea, vomiting, dizziness, etc, were analyzed. RESULTS: The mean reacting time was significantly shorter in group I (4.3 ± 2.1) min than in group II (19.2 ± 8.5) min and in group III (8.5 ± 3.4) min (P < 0.05). The mean reacting time in group III was significantly shorter than in group II (P < 0.05). The total effective rate were similar among the groups (86.7%, 90.0% and 83.3% with a mean decrease in heart ventricular rate by 42.4%, 42% and 41.9% of the baseline level in group I, group II and group III, respectively). The incidence of total side effect was significantly lower in group II (10%) than in group I (16.7%) and group III (20%, P < 0.05). CONCLUSIONS: Intravenous esmolol, amiodarone and diltiazem are all equally effective and safe on controlling rapid ventricular rate in patients with atrial fibrillation during the anesthesia period. Esmolol use is associated with the shortest mean reacting time and amiodarone use is associated with the lowest total side effect rate in this patient cohort.