We report the first genome-wide association study in 1000 bipolar I patients and 1000 controls, with a replication of the top hits in another 409 cases and 1000 controls in the Han Chinese ...population. Four regions with most strongly associated single-nucleotide polymorphisms (SNPs) were detected, of which three were not found in previous GWA studies in the Caucasian populations. Among them, SNPs close to specificity protein 8 (SP8) and ST8 α-N-acetyl- neuraminide α-2,8-sialyltransferase (ST8SIA2) are associated with Bipolar I, with P-values of 4.87 × 10(-7) (rs2709736) and 6.05 × 10(-6) (rs8040009), respectively. We have also identified SNPs in potassium channel tetramerization domain containing 12 gene (KCTD12) (rs2073831, P=9.74 × 10(-6)) and in CACNB2 (Calcium channel, voltage-dependent, β-2 subunit) gene (rs11013860, P=5.15 × 10(-5)), One SNP nearby the rs1938526 SNP of ANK3 gene and another SNP nearby the SNP rs11720452 in chromosome 3 reported in previous GWA studies also showed suggestive association in this study (P=6.55 × 10(-5) and P=1.48 × 10(-5), respectively). This may suggest that there are common and population-specific susceptibility genes for bipolar I disorder.
The response to lithium for the treatment of bipolar disease is variable. This genetic study showed a strong association between variants in
GADL1
and response to treatment in Han Chinese patients ...with bipolar I disease.
Bipolar disorder is a disabling mental illness that is characterized by episodes of both elevated or irritable mood and depression.
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,
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Currently, lithium is the first-line choice for maintenance treatment of bipolar disorder and reduces the risks of relapse and suicide.
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–
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Approximately 80% of patients with bipolar I disorder who are treated with lithium over the long term have at least a partial response,
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and 30% have an excellent response
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,
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with complete remission of symptoms observed in populations of patients of European descent.
Clinical predictors of a good response to lithium treatment have been reported, such as age . . .
More and more organizations have recognized the importance of efficient enterprise knowledge construction, extraction and management. To effectively acquire domain knowledge from experts, a knowledge ...centre that can automatically manage the huge amounts of documents and knowledge is required. In this paper, a knowledge management (KM) model as well as a platform consisting of document keyword extraction (DKE) module, document classification (DC) module, authority reasoning (AR) module and validation process decision (VPD) module are developed for intelligent and automatic management over the manufacturing intellectual properties (IPs) of the automobile industry. In this industry, sophisticated entities are involved in knowledge construction and reuse under the collaborative design environment. A case study is provided to evaluate feasibility and performance of the intelligent knowledge management model. With the training and learning stages, the accuracy and precision of the KM decision modules can be significantly improved. Therefore, in addition to the automobile IP management, it is proven that with the learning mechanism, the proposed intelligent KM approach can be applied to different applications for organizations to efficiently construct and manage domain knowledge .
To verify the association between APOE4 frequency and various dementias in Taiwan Chinese individuals, APOE genotypes were determined in patients with dementia of Alzheimer's type (AD), vascular ...dementia (VD), dementias due to other general medical conditions (OD), and dementia of Alzheimer's type with cerebral vascular disease (mixed type dementia; MD). Only AD patients exhibited higher APOE4 frequency (OR = 2.95, p = 0.001) than controls after Bonferroni correction to control the overall type I error rate for the multiple testing. No such difference was observed among VD, OD, MD and control groups. The lack of association between VD and APOE4 allele frequency suggests that APOE4 allele does not associate with cerebrovascular pathology related dementia in Taiwan Chinese.
Background: A polymorphism locating at position 73 of cystatin C (CST3) exon 1 was suggested to be associated with Alzheimer disease (AD), but with contradictory results. The relationship between the ...CST3 genotype and the cystatin C plasma level in AD remains unknown. Objective: We aim to determine the association between CST3 polymorphism and the plasma levels of cystatin C in AD and nondemented control individuals. Method: The polymorphisms of the CST3 genotype were determined using PCR followed by restriction fragment length polymorphism analysis, and the plasma cystatin C concentrations were quantified by sandwich ELISA in 175 AD and 461 control subjects. Results: Although the CST3A allele frequencies were similar between the two groups, the CST3A/A homozygote was significantly associated with late-onset AD. As expected, the established AD genetic risk factor APOE Ε4 allele was overrepresented in the AD cohort. The plasma cystatin C levels were lower in the AD patients than in the control group. Furthermore, plasma cystatin C levels were associated positively with age and negatively with CST3A allele in the control group. Conclusion: The homozygous CST3A/A genotype confers a risk for AD in Taiwan Chinese. Such an association may be due to the reduced level of cystatin C in the peripheral circulation.
A polymorphism in the cystatin C (CST3) gene was suggested to associate with Alzheimer's disease (AD). In the present study we attempted to determine the association between CST3 polymorphism and AD ...or vascular dementia (VD), and whether such effects are dependent of the APOE4 allele. The polymorphisms of CST3 genotype were determined using polymerase chain reactions (PCR) followed by gel electrophoresis in 124 AD, 70 VD, and 115 control individuals. No statistical difference in CST3B allele frequencies was observed among all three groups. Associations between CST3B/B genotype and AD patients older than 75-year-old, or VD patients younger than 75-year-old were evident. The APOE4 allele alone significantly increased the odds for the developing AD, but not VD. A logistic regression analysis revealed that either CST3 or its interaction with APOE4 were not significant predictors of AD. However, a synergistic association of CST3 and APOE4 alleles was observed in predicting VD patients. These results suggest that CST3 might interact with APOE4 on conferring vascular pathologies.
Twenty-two patients with Parkinson's disease (PD) were studied by clinical evaluation, assessments of dementia and depression, as well as electrophysiologic examinations for blink reflex (BR), ...cortical somatosensory evoked potentials (CSEP), brain stem, and long-latency auditory evoked potentials (BAEP, and LAEP), and cerebrospinal fluid (CSF) assays for monoamine metabolites. Results show that PD patients have a significant decrease of Mini-Mental State Examination (MMSE) scores (
p < 0.05) and an increase of Hamilton Depression Scale (HDS) scores (
p < 0.01), as well as a longer latencies of R2 in BR, N19 and P22 in CSEP, W4 and W5 in BAEP and P300 in LAEP (
p < 0.01), and lower CSF levels of HVA and MHPG (
p < 0.05). The findings suggest a correlation between dementia/depression and mesocorticolimbic and mesostriatocortic dysfunction with dopaminergic and noradrenergic deficiencies in PD patients. Furthermore, parkinsonian dementia parallels the length of duration of the disease, but not the severity of motor disability. Parkinsonian depression parallels both the length of duration of the disease and the severity of motor disability.
Currently, the information and Internet technologies are widely used in modern organizations. Under the trend toward e-manufacturing, most technical knowledge, documents and information are ...transformed from paper-based into electronic formats. In order to improve the efficiency of document security and authentication process management, this paper proposes a heuristic two-phase model for authority and authentication sequence determination for technical documents. In Phase 1 (i.e. authority determination), the keyword extraction and document categorization rules are incorporated into the authority reasoning algorithm to emphasize the importance of technical document contents. In Phase 2, according to the authority reasoning result, six content- and reviewer-oriented indices are proposed for authentication sequence determination. Based on the reasoning models, an integrated prototype system is developed and a demonstration case is also provided to validate the effectiveness of the methodologies. The model and technique explored in this research can be used as the kernel for technical document management and exchange under the computer-integrated manufacturing environment.
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