A genome-wide association study of antidepressant response in Koreans

We conducted a three-stage genome-wide association study (GWAS) of response to antidepressant drugs in an ethnically homogeneous sample of Korean patients in untreated episodes of nonpsychotic unipolar depression, mostly of mature onset. Strict quality control was maintained in case selection, diagnosis, verification of adherence and outcome assessments. Analyzed cases completed 6 weeks of treatment with adequate plasma drug concentrations. The overall successful completion rate was 85.5%. Four candidate single-nucleotide polymorphisms (SNPs) on three chromosomes were identified by genome-wide search in the discovery sample of 481 patients who received one of four allowed selective serotonin reuptake inhibitor (SSRI) antidepressant drugs (Stage 1). In a focused replication study of 230 SSRI-treated patients, two of these four SNP candidates were confirmed (Stage 2). Analysis of the Stage 1 and Stage 2 samples combined (n=711) revealed GWAS significance (P=1.60 × 10^-8) for these two SNP candidates, which were in perfect linkage disequilibrium. These two significant SNPs were confirmed also in a focused cross-replication study of 159 patients treated with the non-SSRI antidepressant drug mirtazapine (Stage 3). Analysis of the Stage 1, Stage 2 and Stage 3 samples combined (n=870) also revealed GWAS significance for these two SNPs, which was sustained after controlling for gender, age, number of previous episodes, age at onset and baseline severity (P=3.57 × 10^-8). For each SNP, the response rate decreased (odds ratio=0.31, 95% confidence interval: 0.20–0.47) as a function of the number of minor alleles (non-response alleles). The two SNPs significantly associated with antidepressant response are rs7785360 and rs12698828 of the AUTS2 gene, located on chromosome 7 in 7q11.22. This gene has multiple known linkages to human psychological functions and neurobehavioral disorders. Rigorous replication efforts in other ethnic populations are recommended.     

Morphometric Study of the Anterior Thalamoperforating Arteries

Objective

To evaluate the morphometry of the anterior thalamoperforating arteries (ATPA).

Methods

A microanatomical study was performed in 79 specimens from 42 formalin-fixed adult cadaver brains. The origins of the ATPAs were divided into anterior, middle, and posterior segments according to the crowding pattern. The morphometry of the ATPAs, including the premammillary artery (PMA), were examined under a surgical microscope.

Results

The anterior and middle segments of the ATPAs arose at mean intervals of 1.75±1.62 mm and 5.86±2.05 mm from the internal carotid artery (ICA), and the interval between these segments was a mean of 3.17±1.64 mm. The posterior segment arose at a mean interval of 2.43±1.46 mm from the posterior cerebral artery (PCA), and the interval between the middle and posterior segments was a mean of 3.45±1.39 mm. The mean numbers of perforators were 2.66±1.19, 3.03±1.84, and 1.67±0.98 in the anterior, middle, and posterior segments, respectively. The PMA originated from the middle segment in 66% of cases. A perforator-free zone was located >2 mm from the ICA in 30.4% and >2 mm from the PCA in 67.1% of cases.

Conclusion

Most perforators arose from the anterior and middle segments, within the anterior two-thirds of the posterior communicating artery (PCoA). The safest perforator-free zone was located closest to the PCA. These anatomical findings may be helpful to verify safety when treating lesions around the PCoA and in the interpeduncular fossa.     

Factors determining early left atrial reverse remodeling after mitral valve surgery

This study aimed to investigate the factors determining early left atrial (LA) reverse remodeling after mitral valve (MV) surgery. The left atrium is frequently dilated in patients with mitral stenosis (MS) or mitral regurgitation (MR). MV surgery usually results in LA volume reduction. However, the factors associated with LA reverse remodeling after MV surgery are not clearly defined. One hundred thirty-eight patients (51 men, 87 women; mean age, 53 years) underwent transthoracic echocardiography before and after MV surgery. Maximal LA volume was measured using the prolate ellipsoid model. The percentage of LA volume change was calculated. The patients were grouped according to age (<50 vs >or=50 years), predominant lesion (pure MR vs some degree of MS), type of surgery (MV repair vs MV replacement), and preoperative rhythm (sinus rhythm vs atrial fibrillation). LA volume decreased from 147+/-93 to 103+/-43 ml (p<0.001) after surgery. LA reverse remodeling was more prominent in patients who were <50 years old (percentage of LA volume change -31.2+/-17.4 vs -18.4+/-19.2, p<0.001), had pure MR (percentage of LA volume change -30.4+/-18.6 vs -17.3+/-18.2, p<0.001), and had a preoperative sinus rhythm (percentage of LA volume change -28.5+/-17.7 vs -20.5+/-20.0, p=0.019). In conclusion, on stepwise multiple regression analysis, preoperative LA volume, predominant lesion, age, and cardiac rhythm were significant predictors of LA reverse remodeling. A larger preoperative LA volume, MR rather than MS, younger age at the time of surgery, and sinus rhythm were important predictors of LA reverse remodeling after MV surgery.     

Is albuminuria an indicator of myocardial dysfunction in diabetic patients without overt heart disease? A study with Doppler strain and strain rate imaging

The aim of this study was to address whether albuminuria could predict myocardial dysfunction in diabetic patients without overt heart disease. We studied 67 patients with normal left ventricular (LV) ejection fraction and no evidence of LV hypertrophy or coronary artery disease (47 patients with type 2 diabetes mellitus and hypertension and 20 patients with hypertension only). Diabetes patients were divided into 3 groups based on albuminuria status: group II = no albuminuria (n = 20, <30 mg/d), group III = microalbuminuria (n = 13, 30-300 mg/d), and group IV = macroalbuminuria (n = 14, >300 mg/d). Twenty patients with hypertension only served as a control group (group I). Conventional 2-dimensional and Doppler echocardiography was done. Peak strain, peak systolic strain rate (SR), and peak diastolic SR of 6 LV segments in the apical views were measured and averaged in each patient. Conventional 2-dimensional parameters such as LV ejection fraction; left atrium volume index; LV mass; deceleration time; and mitral early peak, mitral late peak, myocardial early peak diastolic, and myocardial peak systolic velocities were not different among the 4 groups. However, peak strains were significantly lower in group III (P = .002) and group IV (P < .001) than in group I; and the absolute value of peak systolic SR was lower in group III (P = .033) and group IV (P < .001) than in group I. Furthermore, the value of peak diastolic SR was lower in group IV than in group I (P = .014). In diabetic patients with albuminuria, Doppler strain and SR imaging detected subclinical LV systolic and diastolic dysfunction; and albuminuria was associated with myocardial dysfunction in diabetic patients without overt heart disease.     

Histological and immunohistochemical markers for progression prediction in transurethrally resected high-grade non-muscle invasive bladder cancer

High-grade non-muscle-invasive bladder cancer (Non-MIBC) has a high risk of stage progression to muscle-invasive bladder cancer (MIBC) and could be managed either conservatively by transurethral resection of bladder tumor (TURBT) or more aggressively by radical cystectomy. The selection of patients who may benefit from early radical intervention is a challenge. To define useful prognostic markers for progression, we analyzed clinicopathological features and immunohistochemical expression patterns of E2F1, p27, survivin, p53, EZH2, IMP3, TSC1/hamartin, fatty acid synthase, androgen receptor, 14-3-3σ, MAGEA4, and NY-ESO-1 on 118 cases of high-grade Non-MIBC. During the mean follow-up period of 64.3 months, progression occurred in 18 patients (15.3%). Histologically, large amount of invasive component (> 50%) was noted in 35 cases (29.7%) and was strongly associated with progression. Among the 12 biomarkers, high expressions of E2F1 and nuclear p27 were noted in 46 cases (40.0%) and 14 cases (12.7%), respectively, and were associated with frequent progression. Using multivariate analysis, the proportion of invasive component and high E2F1 expression were independent prognostic factors for the prediction of progression. Our results indicated that large amount of invasive carcinoma component and high expressions of p27 and E2F1 were predictive markers for progression in Non-MIBC. Therefore, we suggest that these parameters, especially proportion of invasive carcinoma component and E2F1 expression, should be evaluated during pathologic examination and considered during selection of the appropriate management strategy for high grade Non-MIBC patients.     

Prenatal Particulate Matter/Tobacco Smoke Increases Infants' Respiratory Infections: COCOA Study

Purpose

To investigate whether prenatal exposure to indoor fine particulate matter (PM_2.5) and environmental tobacco smoke (ETS) affects susceptibility to respiratory tract infections (RTIs) in infancy, to compare their effects between prenatal and postnatal exposure, and to determine whether genetic factors modify these environmental effects.

Methods

The study population consisted of 307 birth cohort infants. A diagnosis of RTIs was based on parental report of a physician''s diagnosis. Indoor PM_2.5 and ETS levels were measured during pregnancy and infancy. TaqMan was used for genotyping of nuclear factor erythroid 2-related factor (Nrf2) (rs6726395), glutathione-S-transferase-pi (GSTP) 1 (rs1695), and glutathione-S-transferase-mu (GSTM) 1. Microarrays were used for genome-wide methylation analysis.

Results

Prenatal exposure to indoor PM_2.5 increased the susceptibility of lower RTIs (LRTIs) in infancy (adjusted odds ratio [aOR]=2.11). In terms of combined exposure to both indoor PM_2.5 and ETS, prenatal exposure to both pollutants increased susceptibility to LRTIs (aOR=6.56); however, this association was not found for postnatal exposure. The Nrf2 GG (aOR=23.69), GSTM1 null (aOR=8.18), and GSTP1 AG or GG (aOR=7.37) genotypes increased the combined LRTIs-promoting effects of prenatal exposure to the 2 indoor pollutants. Such effects of prenatal indoor PM_2.5 and ETS exposure were not found for upper RTIs.

Conclusions

Prenatal exposure to both indoor PM_2.5 and ETS may increase susceptibility to LRTIs. This effect can be modified by polymorphisms in reactive oxygen species-related genes.     

Comparison of gait before and after superficial trunk muscle exercise and deep trunk muscle exercise

[Purpose] The purpose of this study was to examine the effects of superficial trunk muscle and deep trunk muscle exercise on gait. [Subjects] The subjects were 45 young adults who voluntarily consented to participate. The subjects were divided into a control group, a superficial muscle exercise group, and a deep muscle exercise group with 15 participants in each group. [Methods] Each group performed the exercises 5 times a week for 4 weeks. A Gait Analyzer was used to measure the subjects’ gait. A one-way ANOVA was conducted for analysis between each group. [Results] After 4 weeks, the values from right heel contact to foot flat, left foot flat to heel off, right foot flat to heel off, and left heel off to toe off significantly differed among the groups. [Conclusion] The superficial trunk muscle exercise improved stability, such as the period of mid stance during gait. The deep trunk muscle exercise improved mobility, such as heel contact to foot flat and heel off to toe off during gait.Key words: Superficial trunk muscle exercise, Deep trunk muscle exercise, Gait     

Comparisons of shoulder stabilization muscle activities according to postural changes during flexi-bar exercise

[Purpose] The purpose of this study was to compare shoulder stabilization muscle activities according to postural changes during flexi-bar exercise. [Subjects] The subjects included 18 students (10 males, 8 females) at B University. [Methods] The subjects performed the following flexi-bar exercises: 1) medio-lateral oscillation with the 90° shoulder abduction, with the hand in the neutral position; 2) dorso-ventral oscillation with 90° shoulder flexion, with the hand in the neutral position; 3) superior-inferior oscillation with 90° shoulder flexion, with the 80° hand pronation. [Results] The activity of the serratus anterior showed significant differences between each position; however, activities of the upper trapezius and middle trapezius were not significantly different. [Conclusion] The results of this study indicate that posture control is important for selective strengthening of the serratus anterior muscle during flexi-bar exercises.Key words: Flexi-bar exercise, Shoulder stabilization, Muscle activity