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The clinical significance of asymptomatic microbleeds in moyamoya disease remains unclear. The purpose of this study was to clarify the relationship between bypass surgery and the incidence of asymptomatic microbleeds. This retrospective study included 142 adult patients (mean age, 37.7 ± 13.5 years) with moyamoya disease, 36 of whom (25.3%) underwent bypass surgery in childhood. Hemorrhagic onset was diagnosed in 31 patients (21.8%). The incidence of microbleeds was evaluated on T2*-weighted or susceptibility-weighted imaging from 3-T magnetic resonance imaging. The patients were subsequently categorized into MBs (microbleeds) or non-MBs groups. Because previous microbleeds potentially lead to hemorrhage, the MBs group was defined as patients with radiographic evidence of bleeding, including asymptomatic microbleeds and/or hemorrhagic onset. The association of baseline characteristics was evaluated. Asymptomatic microbleeds were detected in 38 patients (26.8%). Of 31 patients with hemorrhagic onset, 18 had microbleeds, whereas 13 had no microbleeds. Therefore, 51 patients (35.9%) were classified into the MBs group. Bypass surgery in childhood (MBs, 7.8% vs. non-MBs, 35.2%; P < 0.01) and age (MBs, 42.9 ± 1.8 years vs. non-MBs, 34.7 ± 1.4 years; P < 0.01) were statistically significant factors associated with microbleeds, but only bypass surgery in childhood remained statistically significant after multivariable adjustment (odds ratio, 0.25; 95% confidence interval, 0.07–0.87; P = 0.03). This study shows the clinical significance of revascularization surgery in childhood associated with a low incidence of asymptomatic microbleeds in adult patients with moyamoya disease. This finding indicates that a newly established bypass can reduce hemodynamic overstress. [ABSTRACT FROM AUTHOR]

• PCA involvement in unilateral MMD occurs exclusively ipsilateral to the anterior lesion. • The homozygous p.R4810K mutation shows the significant effect on PCA involvement. • Clinical outcome of patients with unilateral MMD is generally favorable. • Dyslipidemia and hypertension are independently associated with any residual symptoms. • Cerebral infarction, confounded by hypertension, is associated with any residual symptoms. The characteristics and clinical implications of posterior cerebral artery (PCA) involvement in unilateral moyamoya disease (U-MMD), such as laterality, frequency of the RNF213 p.R4810K mutation, and clinical outcomes, have not been well studied. We analyzed a cohort of 93 patients with U-MMD who participated in the SUPRA Japan study. Clinical characteristics and radiological examinations were collected from medical records. The presence of the p.R4810K mutation was determined using a TaqMan assay. The clinical outcome was assessed using the modified Rankin Scale (mRS). Univariate and multivariate logistic regression analyses were performed to assess the associations. Among the patients with U-MMD, PCA involvement was observed in 60.0 % (3/5) of patients with homozygous mutation, 11.3 % (7/62) of those with heterozygous mutation, and 3.8 % (1/26) of those with wild type, showing a significant linear trend (p < 0.001 for trend). PCA involvement was observed exclusively on the same side as the affected anterior circulation. Dyslipidemia and cerebral infarction at initial onset were independently associated with mRS ≥1. Hypertension was associated with mRS ≥1 and it was also linked to infarction at initial onset, suggesting a potential confounding effect. Although PCA involvement showed a trend for higher mRS, it was not statistically significant. Our findings indicate a gene dose effect of the p.R4810K mutation on PCA involvement, with the homozygous state showing the most significant effect. Both genetic and modifiable factors such as dyslipidemia may influence the progression of U-MMD. [ABSTRACT FROM AUTHOR]

Choroidal anastomosis is a risk factor for hemorrhage in moyamoya disease. One variant of choroidal anastomosis, "transcallosal anastomosis," originates from the medial posterior choroidal artery, and penetrates the corpus callosum to reconstruct the pericallosal artery. We aimed to investigate the prevalence and the bleeding rate of transcallosal anastomosis using sliding thin-slab maximum intensity projection reformatted from magnetic resonance angiography (MRA). This study included 222 patients. We defined transcallosal anastomosis grades (0-2) and the stenosis of the anterior (ACA, 0-2), middle (MCA, 1-3), and posterior cerebral artery (PCA, 0-2) by MRA scores, independently by two coauthors. Grade-2 transcallosal anastomosis was detected in 21 patients (9.5 %). There were no correlations of the incidence of transcallosal anastomosis with previous bypass surgery (P = 0.23). Multivariate analysis revealed a significantly higher incidence in hemorrhagic onset and younger age (odds ratio [OR] 3.77, and 0.97). Transcallosal anastomosis had statistically significant correlation with ACA and PCA scores (P = 0.01 and 0.03), but not with MCA scores (P = 0.1). In multivariate analysis, ACA scores 1 and 2 were significantly higher (OR, 15.44 and 11.17), and PCA score 1 was also higher (OR, 3.07), but PCA score 2 was not. Interrater agreement for judgment of transcallosal anastomosis grade was strong (κ = 0.89). Two patients with Grade-2 transcallosal anastomosis had late hemorrhage in the corpus callosum (bleeding rate: 2.5 % per year). Transcallosal anastomosis may be associated with both advanced ACA and moderate PCA stenosis, and cause hemorrhage at the corpus callosum. [ABSTRACT FROM AUTHOR]

Background Transient neurological deficits are relatively common after direct revascularization surgery for moyamoya disease (MMD). Although recent evidence has revealed the clinical features and pathophysiology, preoperative predictors have remained unclear. This study investigated whether the apparent diffusion coefficient (ADC) in normal-appearing white matter (NAWM) on magnetic resonance imaging could offer a predictor of postoperative transient neurological deficits. Methods This study included adult patients with MMD who underwent superficial temporal artery-middle cerebral artery bypass. Preoperative ADCs were measured in NAWM on ipsilateral hemisphere. Single photon emission computed tomography (SPECT) with 123 I-iodoamphetamine was performed on postoperative days 2-6. Relationships between mean ADC and postoperative transient neurological deficits were assessed. Results Twenty of the 26 subjects (76.9%) experienced transient neurological deficits. Focal hyperemia on postoperative SPECT appeared in 11 of the 20 subjects with postoperative transient neurological deficits and 1 of the 6 subjects without ( P = .12). Mean ADCs in patients with and without postoperative transient neurological deficits were 748.3 ± 12 mm 2 /second × 10 −6 and 679.7 ± 21.9 mm 2 /second × 10 −6 , respectively ( P = .0091). Conclusions Preoperative ADC elevation in NAWM may indicate postoperative transient neurological deficits not only in patients with postoperative hyperemia on SPECT, but also in patients with this pathology. [ABSTRACT FROM AUTHOR]

Background Neurocognitive impairment is one of several unsolved social issues faced by patients with moyamoya disease. Although efforts have been made to investigate cognitive function using neuropsychologic tasks, generalizability has been limited. Here, in a preliminary study, we used structured neuropsychologic tasks to establish a standardized neuropsychologic assessment for adult moyamoya patients with and without difficulty in social independence. Methods Ten patients with neuroradiologically confirmed adult moyamoya disease (3 male, 7 female) participated. Half of all subjects did not have difficulty with social independence (group 1) and the others had (group 2). Group differences were evaluated after basic cognitive abilities and frontal lobe function were tested. Results Although the mean age of group 1 was substantially higher than that of group 2, disease duration did not differ significantly between groups. Means scores for intelligence functions including all subtests for basic cognitive abilities were higher in group 1 compared with group 2. Scores from only 2 frontal lobe evaluation tasks (Trail Making Test B and Theory of Mind) were significantly different between groups. Conclusions This preliminary study provides a profile of neurocognitive dysfunction in adult patients with moyamoya disease using structured neuropsychologic tasks. A broad range of cognitive functions was disrupted particularly in the patients who had difficulty with social independence. To obtain stronger evidence regarding neurocognitive dysfunction in patients with moyamoya disease, a multicenter prospective study is essential. [ABSTRACT FROM AUTHOR]

Abstract: LID are spread on a small scale throughout target area, therefore, evaluation of their overall effect on flood reduction is not straightforward. As one solution dealing with this problem, Yoo et al. (2012) proposed a methodology for quantifying the flood runoff reduction effect of storage facilities by curve number (CN). Introduction of various infiltration or storage facilities causes the decrease in CN, which can be calculated using the runoff. The result derived was summarized in a graph showing the decrease in CN as an effect of the runoff reduction. That is, the runoff reduction effect of infiltration or storage facilities was able to be easily estimated using the derived graph. In this study, LID effects of Gimcheon Pyeonghwa district in Korea was quantified using this method. Additionally, the reduction amount of the runoff volume using the method suggested by Yoo et al. (2012) was compared with that estimated by using SWMM 5.0. As a result of this, the effect of LID facilities was shown similarly in both cases using the methodology used in this study and simulated using SWMM 5.0. This result verified that the methodology was valid even though it is straightforward and simple. [Copyright &y& Elsevier]

Aim: To assess diffusion changes in the remote white matter and areas of white matter with cerebral artery obstruction without magnetic resonance imaging (MRI) evidence of brain parenchymal abnormalities using high b-value diffusion tensor imaging (DTI). Materials and methods: A total of 34 patients with severe unilateral stenosis (≥75%) or occlusion of the middle cerebral artery (MCA) without abnormal brain parenchymal signals at MRI underwent DTI with a b value of 2200 s/mm2 at 3 T. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (eigenvalue λ1) and radial diffusivity (eigenvalue λ23) were measured at the bilateral corona radiata, anterior and posterior limbs of the internal capsule, cerebral peduncle, and pons. Results: The mean FA was significantly lower at the ipsilateral corona radiata and anterior and posterior limbs of the internal capsule than at the contralateral corona radiata and anterior and posterior limbs of the internal capsule (p < 0.05). The mean ADC, λ1 and λ23 were significantly higher at the ipsilateral corona radiata than at the contralateral corona radiata (p < 0.01). The mean λ23 were significantly higher at the ipsilateral anterior and posterior limb of the internal capsule than at the contralateral anterior and posterior limb of the internal capsule (p < 0.05). The mean ADC, λ1 and λ2 3were not significantly different between the ipsilateral cerebral peduncle and pons. Conclusions: High b-value DTI could sensitively reveal diffusion changes in white matter in regions of cerebral artery obstruction without abnormal anisotropy and diffusivity of the remote white matter of patients with severe MCA stenosis or occlusion without MRI evidence of brain parenchymal abnormalities. [Copyright &y& Elsevier]

Molecular diagnosis of complex dual genome mitochondrial disorders is a challenge. It requires the identification of deleterious mutations in one of the ~1,500 nuclear genes and the mitochondrial genome. If the molecular defect is in the mitochondrial genome, quantification of degree of mutation load (heteroplasmy) in affected tissues is important. Due to the extreme clinical and genetic heterogeneity, conventional sequence analysis of the candidate genes one-by-one is impractical, if not impossible. The newly developed massively parallel next generation sequencing (NGS) technique, that allows simultaneous sequence analysis of multiple target genes, when appropriately validated with deep coverage and proper quality controls, can be used as an effective comprehensive diagnostic approach in CLIA certified clinical laboratories. [ABSTRACT FROM AUTHOR]

Summary: Oxidation of lipid substrates is essential for survival in fasting and other catabolic conditions, sparing glucose for the brain and other glucose-dependent tissues. Here we show Steroid Receptor Coactivator-3 (SRC-3) plays a central role in long chain fatty acid metabolism by directly regulating carnitine/acyl-carnitine translocase (CACT) gene expression. Genetic deficiency of CACT in humans is accompanied by a constellation of metabolic and toxicity phenotypes including hypoketonemia, hypoglycemia, hyperammonemia, and impaired neurologic, cardiac and skeletal muscle performance, each of which is apparent in mice lacking SRC-3 expression. Consistent with human cases of CACT deficiency, dietary rescue with short chain fatty acids drastically attenuates the clinical hallmarks of the disease in mice devoid of SRC-3. Collectively, our results position SRC-3 as a key regulator of β-oxidation. Moreover, these findings allow us to consider platform coactivators such as the SRCs as potential contributors to syndromes such as CACT deficiency, previously considered as monogenic. [Copyright &y& Elsevier]

Abstract: Purpose: To review our clinical experience and determine if there are appropriate signs and symptoms to consider POLG sequencing prior to valproic acid (VPA) dosing in patients with seizures. Methods: Four patients who developed VPA-induced hepatotoxicity were examined for POLG sequence variations. A subsequent chart review was used to describe clinical course prior to and after VPA dosing. Results: Four patients of multiple different ethnicities, age 3–18 years, developed VPA-induced hepatotoxicity. All were given VPA due to intractable partial seizures. Three of the patients had developed epilepsia partialis continua. The time from VPA exposure to liver failure was between 2 and 3 months. Liver failure was reversible in one patient. Molecular studies revealed homozygous p.R597W or p.A467T mutations in two patients. The other two patients showed compound heterozygous mutations, p.A467T/p.Q68X and p.L83P/p.G888S. Clinical findings and POLG mutations were diagnostic of Alpers–Huttenlocher syndrome. Conclusion: Our cases underscore several important findings: POLG mutations have been observed in every ethnic group studied to date; early predominance of epileptiform discharges over the occipital region is common in POLG-induced epilepsy; the EEG and MRI findings varying between patients and stages of the disease; and VPA dosing at any stage of Alpers–Huttenlocher syndrome can precipitate liver failure. Our data support an emerging proposal that POLG gene testing should be considered in any child or adolescent who presents or develops intractable seizures with or without status epilepticus or epilepsia partialis continua, particularly when there is a history of psychomotor regression. [Copyright &y& Elsevier]

Abstract: In this paper, we present a haptic prototyping system using a torque-feedback dial, which allows one to estimate the haptic behaviors of the mechanical dial knob in the design process interactively. The system produces various high fidelity haptic effects based on the torque-feedback dial such as jog dial, detent, barrier, and a combination of these behaviors. It can be used to determine the most desirable knob behavior and physical properties for consumer electronics including automobile, washing machine, radio, and game controller. In addition, we have conducted experiments analyzing the haptic behavior''s affect on the user''s emotions and reactions. [Copyright &y& Elsevier]

Arginine is a common substrate for the synthesis of nitric oxide and polyamines that are crucial for placental angiogenesis and growth in mammals. This study was conducted to test the hypothesis that dietary l-arginine supplementation may improve reproductive performance of pregnant gilts. Fifty-two pregnant gilts with body weight (BW) of 166.3 +/- 1.8 kg were housed individually in gestation crates. At d 30 of gestation, gilts were assigned randomly to corn-soybean-based diets supplemented with 1.0% L-arginine-HCl or 1.7% L-alanine (isonitrogenous control). Both diets contained 13.0 MJ metabolizable energy/kg and 12.2% crude protein and were fed to gilts at 1 kg twice daily during gestation. Backfat thickness and BW were measured and blood samples were obtained on 30, 70, 90, and 110 d of gestation. At d 110 of gestation, gilts were transferred to individual farrowing crates. The numbers of total piglets born and born alive, as well as birth weights of piglets, were recorded immediately after farrowing. Throughout the gestation, BW or backfat thickness of gilts did not differ between treatment groups. Plasma urea concentrations were lower in arginine-supplemented than in control gilts at d 90 (P < 0.010) and d 110 (P < 0.001) of gestation. Compared with the control group, arginine supplementation increased the number of pigs born alive by 22% (11.40 vs. 9.37, P = 0.032) and live litter birth weight of piglets by 24% (16.38 vs. 13.19 kg, P = 0.016). This exciting finding provides the first evidence for a marked increase of live-born piglets by 2 per litter through nutritional intervention in gilts. [ABSTRACT FROM AUTHOR]

Abstract: In this article, we review the current methodologies used for the molecular diagnosis of mitochondrial DNA defects. Definition of mitochondrial disorders at the molecular level has been difficult because of both clinical and genetic heterogeneity. Direct DNA analysis for common point mutations and large mtDNA deletions is readily performed and can be done routinely. However, a large number of patients who have the clinical manifestations and muscle pathology findings consistent with mitochondrial DNA disorders do not have detectable common mutations. Additional mutation screening methods are required for the detection of rare and previously undescribed mutations in the mitochondrial genome. [Copyright &y& Elsevier]