SgD-CNV, a database for common and rare copy number variants in three Asian populations

Copy number variants (CNVs) extend our understanding of the genetic diversity in humans. However, the distribution and characteristics of CNVs in Asian populations remain largely unexplored, especially for rare CNVs that have emerged as important genetic factors for complex traits. In the present study, we performed an in-depth investigation of common and rare CNVs across 8,148 individuals from the three major Asian ethnic groups: Chinese (n = 1,945), Malays (n = 2,399), and Indians (n = 2,217) in Singapore, making this investigation the most comprehensive genome-wide survey of CNVs outside the European-ancestry populations to date. We detected about 16 CNVs per individual and the ratio of loss to gain events is ～2:1. The majority of the CNVs are of low frequency (<10%), and 40% are rare (<1%). In each population, ～20% of the CNVs are not previously catalogued in the Database of Genomic Variants (DGV). Contrary to findings from European studies, the common CNVs (>5%) in our populations are not well tagged by SNPs in Illumina 1M and 610K arrays, and most disease-associated common CNVs previously reported in Caucasians are rare in our populations. We also report noticeable population differentiation in the CNV landscape of these Asian populations, with the greatest diversity seen between the Indians and the Chinese.     

Effect of CD4+ CD25+ regulatory T cells on the immune evasion of Schistosoma japonicum

It has been known that parasites developed sophisticated strategies to escape from the host immune assault. More recently, one strategy to induce immune evasion involved CD4⁺CD25⁺ regulatory T cells (Tregs). Mice were infected with Schistosoma japonicum cercariae and then injected intraperitoneally with anti-CD25 monoclonal antibody (anti-CD25 mAb). The results showed that the percentages of CD4⁺CD25⁺ Tregs in mice were expanded by S. japonicum infection, and it could be partially blocked by anti-CD25 mAb. Worm burden in anti-CD25 mAb group (23.17 ± 6.94) was significantly lower than that in infected group (30.17 ± 5.85). The level of interferon gamma was increased with anti-CD25 mAb administration; meanwhile, lower concentration of interleukin 10 was observed in the same group. These results suggest that CD4⁺CD25⁺ Tregs contribute to the escape of S. japonicum from the host immune responses, while anti-CD25 mAb can partially block CD4⁺CD25⁺ Tregs and enhance the protective immunity to the parasite by Th1-type immune response.     

Medical education in Taiwan

Taiwan's medical education system bears a close relationship with its colonial and post-colonial history. Since the late nineteenth century, Western medicine, Chinese medicine, and the practice of the other forms of traditional healing have encountered complex transactions with the state and one another, eventually evolving into the present medical system. Nowadays, the mainstream form of medical education in Taiwan is a 7-year Western program; other forms of medical education include a 5-year graduate program and traditional medicine programs. Challenged by the National Health Insurance that emphasizes cost management since 1995 and criticized by the US National Committee on Foreign Medical Education and Accreditation in 1998, medical education reform was implemented by the Taiwan Medical Accreditation Council established in 2000. The reform tries to bring humanities into various aspects of medical education, including student recruitment, curriculum, licensing, and continuing education. Similar to other modernization projects, the reform transplants the American and British standards to Taiwan. These changes hope to insure the reflective capabilities in physicians on the welfare of patients. However, frustration of current and future physicians may be deepened if the reform is insensitive to local issues or incapable of addressing new global tendencies.     

脾切除术后凝血机制的变化对骨折手术治疗的影响

目的 探讨骨折合并脾破裂的患者,脾脏切除术后凝血功能的异常对骨折治疗的影响.方法 脾切除术后,严密监测凝血功能,尤其是纤维蛋白原(Fbg)和D-二聚体(D-Dimer)及血小板的变化.结果 骨折合并脾破裂的患者,脾切除后,多数会出现高凝状态,表现为血小板数量升高,纤维蛋白原和D-二聚体阳性而影响骨折的治疗.结论 骨折合并脾破裂的患者,脾切除术后,多数会出现高凝状态,必须动态监测凝血功能,主要是血小板,Fbg及D-Dimer,必要时给予药物治疗,以防止血栓形成而影响骨折的手术治疗.     

Intrathecal morphine remotely preconditions the heart via a neural pathway

ABSTRACT:: Central opioid receptor activation triggers cardioprotection against ischemia reperfusion injury, independent of peripheral opioid receptor activity. Using a rodent model of myocardial ischemia reperfusion injury with infarct size as the primary outcome, we tested the hypothesis that spinal opioids confer this beneficial effect via a neural pathway. Intrathecal morphine reduced the infarct size compared with control (23% ± 7% vs. 58% ± 3%, respectively, P < 0.01). Prior antagonism of the autonomic pathway, and the receptors for bradykinin, calcitonin gene-related peptide, and the KATP channel, respectively, abolished this cardioprotection (54% ± 13%, 52% ± 10%, 56% ± 9%, and 49% ± 8%, respectively, P < 0.05). In a second set of experiments, we demonstrated that the increased expression of myocardial phosphorylated-Akt and endothelial nitric oxide synthase induced by intrathecal morphine was blocked by prior administration of hexamethonium. These findings support the notion that spinal opioid receptors stimulate a neural pathway that uses nonopioid neurotransmitters to confer cardioprotection from ischemia reperfusion injury. The use of intrathecal morphine for this purpose has potential clinical application, and it is already being used in the perioperative period to provide prolonged analgesia.     

Collagen-related genes influence the glaucoma risk factor, central corneal thickness

Central corneal thickness (CCT) is a risk factor of glaucoma, the most common cause of irreversible blindness worldwide. The identification of genetic determinants affecting CCT in the normal population will provide insights into the mechanisms underlying the association between CCT and glaucoma, as well as the pathogenesis of glaucoma itself. We conducted two genome-wide association studies for CCT in 5080 individuals drawn from two ethnic populations in Singapore (2538 Indian and 2542 Malays) and identified novel genetic loci significantly associated with CCT (COL8A2 rs96067, p(meta) = 5.40 × 10?13, interval of RXRA-COL5A1 rs1536478, p(meta) = 3.05 × 10??). We confirmed the involvement of a previously reported gene for CCT and brittle cornea syndrome (ZNF469) [rs9938149 (p(meta) = 1.63 × 10?1?) and rs12447690 (p(meta) = 1.92 × 10?1?)]. Evidence of association exceeding the formal threshold for genome-wide significance was observed at rs7044529, an SNP located within COL5A1 when data from this study (n = 5080, P = 0.0012) were considered together with all published data (reflecting an additional 7349 individuals, p(Fisher) = 1.5 × 10??). These findings implicate the involvement of collagen genes influencing CCT and thus, possibly the pathogenesis of glaucoma.     

Association of variants in FRAP1 and PDGFRA with corneal curvature in Asian populations from Singapore

Corneal curvature (CC) is a key determinant of major eye diseases, such as keratoconus, myopia and corneal astigmatism. No prior studies have discovered the genes for CC. Here we report the findings from four genome-wide association studies of CC in 10 008 samples from three population groups in Singapore. Our discovery phase surveyed 2867 Chinese and 3072 Malays, allowing us to identify two loci that were associated with CC variation: FRAP1 on chromosome 1p36.2 and PDGFRA on chromosome 4q12. These findings were subsequently replicated in a validation study involving an additional 2953 Asian Indians and a further collection of 1116 Chinese children. The effect sizes of the identified variants were consistent across all four cohorts, with seven single nucleotide polymorphisms (SNPs) in FRAP1 (lead SNP: rs17036350, meta P-value = 4.06 × 10(-13)) and six SNPs in PDGFRA (lead SNP: rs2114039, meta P-value = 1.33 × 10(-9)) attaining genome-wide significance in the SNP-based meta-analysis of the four studies. This is the first genome-wide survey of CC variation and we have identified two implicated loci in three genetically diverse Asian populations, suggesting the presence of common genetic etiology across multiple populations.