Quantitative assessment of oculomotor function by videonystagmography in multiple system atrophy.

OBJECTIVE: To quantitatively assess oculomotor impairments in multiple system atrophy (MSA) and to explore their correlation with clinical characteristics. METHODS: We recruited 45 patients with MSA, including 21 with dominant ataxia (MSA-C), 24 with dominant parkinsonism (MSA-P), and 40 age-matched healthy controls. Detailed oculomotor performance in the horizontal direction was measured using videonystagmography (VNG). RESULTS: We found that the proportion of abnormal eye movements in patients with MSA was 93.3% (37.7%, 51.1%, 73.3%, 71.1%, and 37.8% on fixation and gaze-holding, without fixation, saccade, smooth pursuit, and optokinetic nystagmus tests, respectively). Patients with MSA-C showed significantly lower gains in smooth pursuit test and optokinetic nystagmus test, and a higher incidence of hypermetria in the saccade test than patients with MSA-P (all P < 0.05). No oculomotor deficits were correlated with age, age of onset, sex, disease duration, or Unified Multiple System Atrophy Rating Scale (USMARS) (all r < 0.25, P > 0.1). CONCLUSIONS: An extremely high incidence of oculomotor impairments could be observed using VNG in both the MSA-C and MSA-P subtypes, although there were some differences between them. SIGNIFICANCE: A comprehensive oculomotor examination could serve as a valuable tool in the diagnostic workup of patients with MSA.

Assessment the effect of genomic selection and detection of selective signature in broilers.

Due to high selection advances and shortened generation interval, genomic selection (GS) is now an effective animal breeding scheme. In broilers, many studies have compared the accuracy of different GS prediction methods, but few reports have demonstrated phenotypic or genetic changes using GS. In this study, the paternal chicken line B underwent continuous selection for 3 generations. The chicken 55 k SNP chip was used to estimate the genetic parameters and detect genomic response regions by selective sweep analysis. The heritability for body weight (BW), meat production, and abdominal fat traits were ranged from 0.12 to 0.38. A high genetic correlation was found between BW and meat production traits, while a low genetic correlation (<0.1) was found between meat production and abdominal fat traits. Selection resulted in an increase of about 516 g in BW and 140 g in breast muscle weight. Percentage of breast muscle and whole thigh were increased 0.8 to 1.5%. No change was observed in abdominal fat percentage. The genomic estimated breeding value advances was positive for BW and meat production (except whole thigh percentage), while negative for abdominal fat percentage. By selective sweep analysis, 39 common chromosomal regions and 102 protein coding genes were found to be influenced, including MYH1A, MYH1B, and MYH1D of the MYH gene family. Tight junction pathway as well as myosin complex related terms were enriched. This study demonstrates the effective use of GS for improvements in BW and meat production in chicken line B. Further, genomic regions, responsive to intensive genetic selection, were identified to contain genes of the MYH family.

Pharmacokinetics of pilsicainide hydrochloride for injection in healthy Chinese volunteers: a randomized, parallel-group, open-label, single-dose study.

BACKGROUND: Pilsicainide hydrochloride is a class IC antiarrhythmic agent used for the treatment of supraventricular and ventricular arrhythmias and atrial fibrillation. OBJECTIVE: The objective of the present study was to determine the pharmacokinetics (PK) of a pilsicainide hydrochloride injection in healthy Chinese adults. The study was conducted to meet China State Food and Drug Administration requirements for the marketing of the new generic formulation of pilsicainide hydrochloride. METHODS: This Phase I, randomized, parallel-group, open-label, single-dose PK study was conducted in healthy Chinese volunteers. Subjects were randomized to receive a single dose of 0.25-, 0.50-, and 0.75-mg/kg pilsicainide hydrochloride with a 10-minute intravenous infusion. Serial blood and urine samples were collected up to 24 hours after dosing; drug concentrations in plasma and urine were then determined by using LC-MS/MS. The PK parameters of pilsicainide were calculated from the plasma concentration-time data according to noncompartmental methods. Safety profile was evaluated by monitoring adverse events, clinical laboratory parameters, and the results of 12-lead ECGs. RESULTS: Thirty healthy volunteers (mean [SD] age, 28.0 [4.95] years; weight, 59.3 [6.51] kg; height, 165.0 [7.25] cm; body mass index, 21.7 [1.94] kg/m(2)) were randomly divided into 3 groups, each consisting of 5 men and 5 women. After single-dose intravenous administration of 0.25, 0.50, and 0.75 mg/kg of pilsicainide hydrochloride, mean Cmax was 0.34 (0.11), 0.54 (0.15), and 1.05 (0.19) µg/mL, respectively; AUC0-24 was 0.76 (0.12), 1.61 (0.37), and 2.61 (0.46) h · µg/mL; and AUC0-∞ was 0.79 (0.13), 1.71 (0.46), and 2.72 (0.50) h · µg/mL. The ranges for t½z, CL, and Vz were 5.19 to 5.98 hours, 4.73 to 5.44 mL/min/kg, and 2.23 to 0.58 L/kg, respectively. The mean urinary recovery rate within 24 hours was 75.0% (12.0%), 65.0% (19.2%), and 66.4% (14.1%). Men and women had significantly different AUC0-24 values in the 0.50-mg/kg dose group (P = 0.044), and Vz showed significant differences between men and women in all 3 dose groups (P = 0.001). According to ECG parameters, PR intervals were significantly prolonged after administration at all 3 doses (P = 0.034, P < 0.001, and P = 0.034); no significant changes were seen in QRS width, QTc interval, or other parameters. CONCLUSIONS: Pilsicainide hydrochloride demonstrated linear PK, and the increase in the exposure of pilsicainide (AUC0-24 and AUC0-∞) was dose proportional after single doses of 0.25, 0.50, and 0.75 mg/kg. All 3 pilsicainide hydrochloride doses were well tolerated in these Chinese volunteers. ChiCTR-ONC-13003546.