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Evidence has shown that interleukin-18 (IL-18) has both antitumor and pro-tumor effects in various types of leukemia. The current study aimed at investigating the contribution of IL-18 polymorphisms to the risk of childhood acute lymphocytic leukemia (ALL) in Taiwan.IL-18 promoter -656 (rs1946519), -607 (rs1946518), and -137 (rs187238) genotypes of 266 childhood ALL cases and 266 controls were determined by polymerase chain reaction-restriction fragment length polymorphism methodology.The distributions of genotypic and allelic frequencies of IL-18 rs1946519, rs1946518 or rs187238, were not significantly different between childhood ALL cases and controls (all p0.05). However, in the stratification analysis among the cases, IL-18 rs187238 GC and CC genotypes were associated with increased childhood ALL risk and shorter survival (OR=4.19 and 2.93, 95%CI=2.04-8.64 and 1.19-7.23, p=0.0001 and 0.0250, respectively). No association was found with rs1946519 and rs1946518 (all p0.05).IL-18 rs187238 GC and CC genotypes can serve as predictors for childhood ALL prognosis among Taiwanese. Validation in larger and various populations can greatly extend the feasibility of this novel predictor.

A novel thermal-constant blood-feeder covered with a perforated film and using pig blood was developed for rearing Aedes aegypti (L.) (Diptera: Culicidae). The perforated film was used as a substitute for the membrane or parafilm that is normally used in conventional blood-feeders to prevent the mosquitoes from directly contacting the blood. The efficiency of this perforated blood feeder was assessed by using live mice and comparing the engorgement rate of female mosquitoes and their demographic parameters. In a no-choice test, no significant differences were observed in the engorgement rates and fecundity between females fed on perforated feeders containing pig blood and those fed on live mice. In a three-minute-long free-choice test, the accumulated engorgement rate was significantly higher in mosquitoes feeding on the perforated feeders than in those feeding on live mice. The demographic characteristics indicated that mosquitoes fed on the perforated feeder containing pig blood had a higher immature survival rate and prolonged adult male and female longevity. Although a lower intrinsic rate of increase and lower finite rate of increase were observed when female adults fed on the perforated feeder, computer projection of the population growth was comparable using both blood sources. Massrearing analysis showed that the perforated blood feeder was much more cost-effective than using live mice. These results demonstrate that the perforated blood feeder containing pig blood is more effective and cost efficient than using live mice for maintaining and mass rearing of mosquitoes in the laboratory.

Background: Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary syndrome that predominantly affects women. Its pathophysiology remains unclear but connective tissue disorders (CTD) and other vasculopathies have been observed in many SCAD patients. A genetic component for SCAD is increasingly appreciated, although few genes have been robustly implicated. We sought to clarify the genetic cause of SCAD using targeted and genome-wide methods in a cohort of sporadic cases to identify both common and rare disease-associated variants. Methods: A cohort of 91 unrelated sporadic SCAD cases was investigated for rare, deleterious variants in genes associated with either SCAD or CTD, while new candidate genes were sought using rare variant collapsing analysis and identification of novel loss-of-function variants in genes intolerant to such variation. Finally, 2 SCAD polygenic risk scores were applied to assess the contribution of common variants. Results: We identified 10 cases with at least one rare, likely disease-causing variant in CTD-associated genes, although only one had a CTD phenotype. No genes were significantly associated with SCAD from genome-wide collapsing analysis, however, enrichment for TGF (transforming growth factor)-β signaling pathway genes was found with analysis of 24 genes harboring novel loss-of-function variants. Both polygenic risk scores demonstrated that sporadic SCAD cases have a significantly elevated genetic SCAD risk compared with controls. Conclusions: SCAD shares some genetic overlap with CTD, even in the absence of any major CTD phenotype. Consistent with a complex genetic architecture, SCAD patients also have a higher burden of common variants than controls.

Background/aim This study investigated whether genetic variations in cyclin D1 (CCND1) are associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). Materials and methods A total of 266 childhood ALL cases and 266 healthy controls were genotyped for CCND1 rs9344 and rs678653. Results There was a significant difference in the genotypic distribution of rs9344 between childhood ALL patients and healthy controls (p=0.0077). Compared to the AA genotype, AG and GG genotypes were associated with significantly decreased risks of childhood ALL with odds ratio (OR) of 0.65 [95% confidence interval (CI)=0.44-0.94, p=0.0234] and 0.45 (95%CI=0.26-0.78, p=0.0040), respectively. Supporting this, allelic frequency distributions between childhood ALL patients and controls was significantly different (OR=0.68, 95%CI=0.53-0.88, p=0.0025). There was no significant difference in the genotypic and allelic distributions of rs678653 between cases and controls. Conclusion CCND1 rs9344, but not rs678653, may serve as a predictive marker of susceptibility for childhood ALL.

Background/aim The roles of microRNAs (miRNAs) in tumorigenesis have attracted a lot of attention. The current study aimed at examining the association of the miR-196a-2 rs11614913 genotypes with susceptibility to childhood acute lymphoblastic leukemia (ALL) in Taiwan. Materials and methods This case-control investigation recruited 266 patients with childhood ALL and 266 healthy controls, and the miR-196a-2 rs11614913 genotypes of each participant were examined via the polymerase chain reaction-restriction fragment length polymorphism methodology. Results The frequency of miR-196a-2 C allele in controls was 0.440 compared with 0.423 in ALL patients. In addition, there was no significant association between CT or CC genotypes with susceptibility to childhood ALL (OR=0.89 and 0.89, 95%CI=0.60-1.30 and 0.54-1.45, p=0.5427 and 0.6302). Furthermore, the frequencies of miR-196a-2 polymorphisms were not associated with age, gender and clinical outcomes in ALL cases. Conclusion The miR-19a-2 genotypes are not associated with susceptibility to childhood ALL in Taiwan.

Background Green lacewings (Neuroptera: Chrysopidae) are important beneficial insects that can be raised on artificial diets for culturing experimental lines. An encapsulation method for embedding a core material within a sealed shell to prevent evaporation and biological contamination is crucial for providing food to these predatory insects. Results This study presents a new encapsulation process to mass produce a core-shell microcapsule diet for rearing Mallada basalis (Walker) (Neuroptera: Chrysopidae). This new process provided consistent quality control and effectiveness of the microcapsule diet (742.1 ± 11.3 μm in diameter and 44.2 ± 1.9 μm in shell thickness). Furthermore, significant differences were measured in larval development (24.0 ± 0.3 vs. 20.1 ± 0.6 days) and fecundity (465 ± 65.05 vs. 678 ± 54.91 eggs) on comparing the development of M. basalis larvae fed the old and new diets. Survival rates increased in both single- and group-rearing tests for adults fed the new diet during the larval stages. Neither diet affected predation rates for M. basalis larvae preying on nymphs of Aphis gossypii Glover (Hemiptera: Aphididae) and Bemisia argentifolli Bellows and Perring (Hemiptera: Aleyrodidae). Conclusion Compared with the old process, the new encapsulation process requires reduced effort during preparation, and reduces the weight, cost and space occupied by the equipment. The results of this study suggest that this new spherical microcapsule artificial diet is suitable for group-rearing of M. basalis and may be appropriate for mass-rearing of other types of carnivorous insects. © 2019 Society of Chemical Industry.

BACKGROUND: Sexual health is a taboo issue in some societies. Limited assessments were conducted during nursing care in mental health services. It is unknown whether psychiatric nurses’ competencies would be enhanced through short training courses. OBJECTIVE: The present study employed a quasi-experimental design to evaluate the effectiveness of an 8-hour sexual health care training for psychiatric nurses to improve sexual health knowledge, attitude, and self-efficacy in a teaching psychiatric hospital in southern Taiwan. METHOD: Volunteered psychiatric nurses were randomly assigned to the experimental or control group. The 8-hour training program contained sexual health knowledge and attitudes, case discussion, role play, and sexual identity or harassment issues. Each nurse received a pretest and a posttest in the 1-month period between August and September 2019. Descriptive and multivariate statistical analyses were used to evaluate the effects. RESULTS: Among the 75 psychiatric nurses, 43 were in the control group and 32 were in the experimental group. The two groups were not significantly different in the working year, gender, education, marriage, and other psychosocial variables. After the training, the overall performance of sexual health care knowledge, attitudes, and self-efficacy of the experimental group improved significantly than the controls. CONCLUSIONS: The sexual health care training program enhanced psychiatric nurses’ confidence and generally improved their sexual knowledge and attitudes. It is suggested that sexual health care needs to be highlighted during in-job training to augment the well-being and life quality of psychiatric patients.

This study investigated whether genetic variations in cyclin D1 (CCND1) are associated with susceptibility to childhood acute lymphoblastic leukemia (ALL).A total of 266 childhood ALL cases and 266 healthy controls were genotyped for CCND1 rs9344 and rs678653.There was a significant difference in the genotypic distribution of rs9344 between childhood ALL patients and healthy controls (p=0.0077). Compared to the AA genotype, AG and GG genotypes were associated with significantly decreased risks of childhood ALL with odds ratio (OR) of 0.65 [95% confidence interval (CI)=0.44-0.94, p=0.0234] and 0.45 (95%CI=0.26-0.78, p=0.0040), respectively. Supporting this, allelic frequency distributions between childhood ALL patients and controls was significantly different (OR=0.68, 95%CI=0.53-0.88, p=0.0025). There was no significant difference in the genotypic and allelic distributions of rs678653 between cases and controls.CCND1 rs9344, but not rs678653, may serve as a predictive marker of susceptibility for childhood ALL.

In Taiwan, The increase in life expectancy in Taiwan has increased the incidents of age-related problems among patients with mental illness. Therefore, the needs related to long-term care in mental health are significantly important. These needs include: (1) reducing stigmatization; (2) reducing the physical and economic burden of caregivers; (3) constructing a comprehensive, long-term care service system; and (4) developing assessment tools suitable to the long-term care of patients with mental illness. Moreover, six dilemmas in meeting long-term care needs were identified. These dilemmas include: (1) lack of a model of continuous care and of a platform for integrating hospital and community resources; (2) poor / inadequate service quality provided by certain community rehabilitation institutions; (3) the needs of patient/family centered care; (4) the persistence of stigma and misunderstanding; (5) the heavy burdens borne by family members providing long-term care; and (6) the disconnect between subsequent needs and the disability assessment system. Policy suggestions provided in this article include: (1) establish an inclusive platform for mental health long-term care information and resource integration; (2) construct long-term care centers for patients with mental health conditions; (3) train adequate manpower to provide long-term care services to these patients; and (4) promote community inclusiveness for these patients. In order to enter the era of long-term mental health care, government policy should target long-term care programs to meet the needs of patients with mental health conditions. These programs should include seamlessly integrating services into the long-term mental health care system and the care resources of community mental health, developing suitable assessment tools, establishing a multidisciplinary team of long-term care professionals to provide mental health care.精神病人長期照顧需求、困境與政策建議.國人平均餘命增加，精神病人也面臨老化，其所需要的長期照顧議題更顯重要。精神病人在長期照顧方面有幾點需求：（一）抗拒污名化；（二）降低照顧者身心與經濟負荷等需求；（三）建構完整長期照顧服務體制；（四）發展合適精神病人長期照顧評估工具。因此在滿足精神病人的需求時，其長期照顧困境有以下幾點：（一）缺乏醫院到社區的連續性照護模式及資源的整合平台；（二）社區復健機構不足及良莠不齊；（三）需以精神病人與其家庭的需求為中心；（四）污名化與誤解仍存在；（五）家屬仍承受長期照顧精神病人的責任重擔；（六）身心障礙評估銜接後續需求的制度尚未建立完整。對應提出幾點政策建議：（一）設置專屬精神長期照顧資訊平台並作資源整合；（二）設置精神病人為主的長期照顧中心部門；（三）培訓足夠的精神長期照顧服務人力；（四）增進精神病人社區融合。期望政府未來政策可以針對精神病人需求，提供長期照顧服務無縫接軌，整合精神社區長期照顧資源，提供合適長期照護評估工具與建置各類精神長期照顧專業人才，邁向精神長期照顧新紀元。.

BACKGROUND/AIM The association of matrix metalloproteinase-2 (MMP-2) genotypes with adult leukemia has been reported only once, but never for childhood leukemia. This study aimed to determine the role of MMP-2 promoter -1306 (rs243865) and -735 (rs2285053) genotypes in childhood leukemia risk. MATERIALS AND METHODS This case-control study included 266 patients and 266 age- and gender-matched healthy controls. The polymorphic sites of MMP-2 were genotyped by typical polymerase chain reaction-restriction fragment length polymorphism. RESULTS The CC, CT and TT of rs243865 genotype were 75.2, 23.7 and 1.1% in the case group and 69.2, 28.9 and 1.9% in the control group, respectively. The CT and TT genotypes caused a 0.75- and 0.55-fold increase in the risk of childhood leukemia, respectively. There was no differential distribution of rs2285053 genotypes. Allelic frequency analysis showed that the T allele of MMP-2 promoter -1306 and -735 conferred lower susceptibility than the C allele. CONCLUSION The MMP-2 promoter genotypes play a minor role in determining personal susceptibility to childhood leukemia among the Taiwanese.

Purpose A growing body of evidence shows an association between DNA repair protein genotypes and susceptibility to various cancers. However, few studies have assessed the contribution of the genotype of XRCC3, a homologous repair gene, to the occurrence or prognosis of childhood acute lymphoblastic leukemia (ALL). In this study, we investigated the contribution of seven XRCC3 polymorphisms to childhood ALL. Patients and methods We recruited 266 patients with childhood ALL and 266 healthy controls. Genomic DNA was isolated from peripheral blood samples. The XRCC3 rs1799794, rs45603942, rs1799796, rs861530, rs28903081, rs861539, and rs3212057 polymorphic genotypes of each subject were determined through conventional polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results Genotypes with the rs861539 polymorphism were significantly associated with the risk of childhood ALL. The allelic distribution analyses suggested a significant association between the T allele at rs861539 with an increased risk of childhood ALL in the Taiwanese population. Polymorphic variants of XRCC3 at rs3212057 or rs28903081 did not exist in the study population. XRCC3 rs1799794, rs45603942, rs1799796, and rs861530 were not significantly associated with the risk of childhood ALL in the Taiwanese population. Conclusion Our findings suggest that XRCC3 genotypes with polymorphisms at rs861539 may play a role in determining individual susceptibility to childhood ALL in this Taiwanese population. The polymorphism may be a potential detector and predictor of childhood ALL.

Prostacyclin agonists that bind the prostacyclin receptor (IP) to stimulate cAMP synthesis are effective vasodilators for the treatment of idiopathic pulmonary arterial hypertension (IPAH), but this signaling may occur through nuclear peroxisome proliferator-activated receptor-γ (PPARγ). There is evidence of scant IP and PPARγ expression but stable prostanoid EP4 receptor (EP4) expression in IPAH patients. Both IP and EP4 functionally couple with stimulatory G protein (Gs), which activates signal transduction. We investigated the effect of an EP4-specific agonist on pulmonary arterial remodeling and its regulatory mechanisms in pulmonary arterial smooth muscle cells (PASMCs). Immunoblotting evealed IP, EP4, and PPARγ expression in human pulmonary arterial hypertension (PAH) and monocrotaline (MCT)-induced PAH rat lung tissue. Isolated PASMCs from MCT-induced PAH rats (MCT-PASMCs) were treated with L-902,688, a selective EP4 agonist, to investigate the anti-vascular remodeling effect. Scant expression of IP and PPARγ but stable expression of EP4 was observed in IPAH patient lung tissues and MCT-PASMCs. L-902,688 inhibited IP-insufficient MCT-PASMC proliferation and migration by activating PPARγ in a time- and dose-dependent manner, but these effects were reversed by AH-23848 (an EP4 antagonist) and H-89 [a protein kinase A (PKA) inhibitor], highlighting the crucial role of PPARγ in the activity of this EP4 agonist. L-902,688 attenuated pulmonary arterial remodeling in hypoxic PAH mice and MCT-induced PAH rats; therefore, we conclude that the selective EP4 agonist L-902,688 reverses vascular remodeling by activating PPARγ. This study identified a novel EP4-PKA-PPARγ pathway, and we propose EP4 as a potential therapeutic target for PAH.

Background/Aim: Mounting evidence has shown that miRNAs play a critical role in the regulation of hematopoiesis of cell proliferation and apoptosis as well as in tumorigenesis. The miR146a rs2910164 polymorphism, which is closely responsive for its expression, has been reported to associate with the risk of several solid cancers. The study aimed at examining the association of the it with susceptibility to childhood acute lymphoblastic leukemia (ALL) in Taiwan. Materials and Methods: We recruited 266 patients with childhood ALL and 266 healthy controls, and rs2910164 genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism methodology. Results: The allele G was associated with decreased childhood ALL risk (OR=0.66, 95%CI=0.52-0.85, p=0.0011). Consistently, the GG genotype was associated with a decreased susceptibility (OR=0.40, 95%CI=0.23-0.67, p=0.0004). Patients with CG and GG genotypes were of earlier onset than those with CC genotype (p=0.0255 and p=0.0001). Conclusion: MiR146a rs2910164 G allele serves as a protective marker for childhood ALL in Taiwan.

Oxidative stress may play critically important roles in the etiology of Parkinson's disease (PD). 6-Hydroxydopamine (6-OHDA) is a physiological neurotoxin reported to induce oxidative-induced apoptosis of dopaminergic neurons in PD mice models. Valproic acid (VPA), a clinical mood stabilizer, is a HDAC inhibitor with neuroprotective capacities. In the study, we aim at examining the feasibility of VPA as a protector for dopaminergic neurons against damage from 6-OHDA, and the intracellular mechanisms. The 6-OHDA-induced neurotoxicity to the human dopaminergic cell line SH-SY5Y was applied for examining VPA protective effects. Pretreatment with VPA was able to improve cell viability and reduce 6-OHDA-induced reactive oxygen species. Furthermore, a significant suppression of apoptotic caspases including cleaved caspase-3, caspase-7, and caspase-9 was observed. The results also revealed VPA decreased the 6-OHDA-induced Bax/Bcl2 ratio, as measured at protein level. These novel findings indicate that VPA may be capable of protecting the SH-SY5Y dopaminergic neuronal cells from 6-OHDA-induced toxicity via the deceasing of apoptotic caspases (cleaved caspase-3, caspase-7, and caspase-9) and reducing of the Bax/Bcl2 ratio. Very possibly, VPA could serve as not only a mood stabilizer but also a potential antidote for PD prevention.

Background/aim Cells suffer from oxidative DNA damage which leads to the accumulation of 8-oxoguanine (8-oxoG) adducts in our genome that can become carcinogenic. The human 8-oxoG DNA glycosylase 1 (hOGG1) plays a central role in repairing these 8-oxoGs via the base excision repair pathway. Mounting evidence has suggested that hOGG1 polymorphisms may affect the activity of hOGG1 and serve as genomic markers for the prediction of personal susceptibility to several cancers. To determine whether the commonly examined hOGG1 rs1052133 (Ser326Cys) polymorphism is associated with the risk of childhood acute lymphoblastic leukemia (ALL) among Taiwanese children, we genotyped the hOGG1 rs1052133 (Ser326Cys) in 266 cases and 266 controls. Results The distributions of the GG, CG and CC genotypes at the hOGG1 rs1052133 were 49.2, 39.1 and 11.7% in the control group and 48.1, 36.1 and 15.8% in the case group (p=0.3656). The combined genotypes CG+CC were not associated with increased risk of childhood ALL (odds ratio [OR]=1.05, 95% confidence interval [CI]=0.74-1.47, p=0.7947). Conclusion The hOGG1 rs1052133 polymorphism is not associated with susceptibility to childhood ALL in the Taiwanese population.

AIM Up-regulation of metalloproteinase (MMPs) proteins have been shown in various types of solid cancers and the genotype of MMP1 has been associated with the risk of solid cancers. However, the contribution of MMP1 genotype to leukemia has never been investigated to our knowledge. Therefore, in this study we aimed to evaluate the contribution of the genotypic variants in the promoter region of MMP1 to childhood acute lymphoblastic leukemia (ALL) risk in Taiwan. MATERIALS AND METHODS In this case-control study, 266 patients with childhood ALL and 266 non-cancer controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS The distribution of 2G/2G, 1G/2G and 1G/1G for MMP1 promoter rs1799750 genotype was 49.2%, 39.5% and 11.3% in the childhood ALL group and 36.8%, 43.6% and 19.5% in the non-cancer control group, respectively (p for trend=0.0046), significantly differentially distributed between childhood ALL and control groups. The carrier comparisons in dominant and recessive models also support the findings that 1G appears to be the protective allele in childhood ALL. In genotype and gender interaction analysis, it was found that boys carrying the MMP1 rs1799750 1G/2G or 1G/1G genotypes had lower odds ratios(ORs) of 0.68 and 0.43 [95% confidence intervals (CI)=0.47-0.98 and 0.26-0.73, p=0.0395 and 0.0013, respectively] for childhood ALL than those carrying the 2G/2G genotype. Analysis of genotype inaction with age of onset age showed those aged less than 3.5 years at onset carrying the 1G/2G or 1G/1G genotypes had lower ORs (0.0183 and 0.0004, respectively) for childhood ALL, but there was no such difference for those having an age at onset of 3.5 years or more. CONCLUSION Our results indicate that the MMP1 rs1799750 1G allele is a protective biomarker for childhood ALL.

The association of matrix metalloproteinase-2 (MMP-2) genotypes with adult leukemia has been reported only once, but never for childhood leukemia. This study aimed to determine the role of MMP-2 promoter -1306 (rs243865) and -735 (rs2285053) genotypes in childhood leukemia risk.This case-control study included 266 patients and 266 age- and gender-matched healthy controls. The polymorphic sites of MMP-2 were genotyped by typical polymerase chain reaction-restriction fragment length polymorphism.The CC, CT and TT of rs243865 genotype were 75.2, 23.7 and 1.1% in the case group and 69.2, 28.9 and 1.9% in the control group, respectively. The CT and TT genotypes caused a 0.75- and 0.55-fold increase in the risk of childhood leukemia, respectively. There was no differential distribution of rs2285053 genotypes. Allelic frequency analysis showed that the T allele of MMP-2 promoter -1306 and -735 conferred lower susceptibility than the C allele.The MMP-2 promoter genotypes play a minor role in determining personal susceptibility to childhood leukemia among the Taiwanese.

Purpose A growing body of evidence shows an association between DNA repair protein genotypes and susceptibility to various cancers. However, few studies have assessed the contribution of the genotype of XRCC3, a homologous repair gene, to the occurrence or prognosis of childhood acute lymphoblastic leukemia (ALL). In this study, we investigated the contribution of seven XRCC3 polymorphisms to childhood ALL. Patients and methods We recruited 266 patients with childhood ALL and 266 healthy controls. Genomic DNA was isolated from peripheral blood samples. The XRCC3 rs1799794, rs45603942, rs1799796, rs861530, rs28903081, rs861539, and rs3212057 polymorphic genotypes of each subject were determined through conventional polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results Genotypes with the rs861539 polymorphism were significantly associated with the risk of childhood ALL. The allelic distribution analyses suggested a significant association between the T allele at rs861539 with an increased risk of childhood ALL in the Taiwanese population. Polymorphic variants of XRCC3 at rs3212057 or rs28903081 did not exist in the study population. XRCC3 rs1799794, rs45603942, rs1799796, and rs861530 were not significantly associated with the risk of childhood ALL in the Taiwanese population. Conclusion Our findings suggest that XRCC3 genotypes with polymorphisms at rs861539 may play a role in determining individual susceptibility to childhood ALL in this Taiwanese population. The polymorphism may be a potential detector and predictor of childhood ALL.

Introduction: The beneficial effects of combined psychosocial and pharmacological treatments for bipolar disorder have been widely documented. However, little research has specifically looked at bipolar II disorder (BP-II), despite it being the most common variant. Methods: This study used a matched-pairs two-group pretest–posttest design to compare the effectiveness of the 10-session weekly “BalancingMySwing” (BMS) program with treatment as usual in a Han Chinese cohort with bipolar II disorder. Twenty-four participants from a medical center in southern Taiwan with a DSM-IV diagnosis of BP-II were purposively recruited and divided into two matched-pair groups for treatment feasibility. Primary outcome indicators were medication adherence and mood symptoms, which were assessed at baseline and posttreatment. Medication adherence was assessed using the self-reported Medication Adherence Rating Scale (MARS). Mood symptoms were assessed by a blinded rater using the 11-item Young Mania Rating Scale (YMRS) and 17-item Hamilton Depression Rating Scale (HDRS). Results: After 10 weeks, a significant group × time interactions for the MARS scores indicated that improvements in medication adherence were greater in the BMS group than in the Treatmentas- Usual (TAU) group. However, there were no significant time effects or group differences for the HDRS or the YMRS scores in either group. Conclusion: Our data support the potential beneficial effects of the nurse-led psychoeducational program on medication adherence in Taiwanese Han Chinese with BP-II. Several limitations and barriers to implementation that might confound results are discussed. Future studies with larger samples and longer follow-ups are needed.

BACKGROUND/AIM The matrix metalloproteinases (MMPs) are important in inflammation and carcinogenesis, and the genotypic role of MMP7 has never been examined in leukemia to date. Therefore, in this study we aimed to evaluate the contribution of the genotypic variants in the promoter region of MMP7 (A-181G and C-153T) to childhood acute lymphoblastic leukemia (ALL) risk in Taiwan. MATERIALS AND METHODS In this case-control study, 266 patients with childhood ALL and 266 non-cancer controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS The distribution of AA, AG and GG for MMP7 promoter A-181G genotype was 83.5, 12.0 and 4.5% in the childhood ALL group and 89.8%, 9.4 and 0.8% in the non-cancer control group, respectively (p for trend=0.0134), significantly differentially distributed between childhood ALL and control groups. The comparisons in allelic frequency distribution also support the findings that G appears to be the risky allele in childhood ALL. In genotype and gender interaction analysis, it was found that boys carrying the MMP7 A-181G GG and AG+GG genotypes had 9.05- and 2.45-fold odds ratios (ORs) (p=0.0135 and 0.0142, respectively) for childhood ALL compared to those carrying wild-type AA genotype. But these differences were not found in girls. Analysis of genotype interaction with age of onset age showed those aged less than 3.5 years at onset carrying the GG or AG+GG genotypes also had elevated ORs of 8.79- and 2.04-fold (p=0.0150 and 0.0413, respectively) for childhood ALL, but there was no such difference for those having an age at onset of 3.5 years or more. CONCLUSION Our results indicate that the MMP7 A-181G genotype interacts with age and gender and may serve as an early and predictive biomarker for childhood ALL.

Prostacyclin agonists that bind the prostacyclin receptor (IP) to stimulate cAMP synthesis are effective vasodilators for the treatment of idiopathic pulmonary arterial hypertension (IPAH), but this signaling may occur through nuclear peroxisome proliferator-activated receptor-γ (PPARγ). There is evidence of scant IP and PPARγ expression but stable prostanoid EP

Bipolar disorder (BD) is a severe mental illness that is characterized by chronicity, pervasive instability, and relatively high rates of recurrence and suicide. Current evidence supports that adverse circles among hereditary and genetic factors, neuroinflamation, and social rhythm constitute a crucial etiology. Pharmacological treatment is the first priority for BD patients during the acute stage. Pharmacological and psychosocial treatments should be combined during the maintenance stage in order to help patients self-manage medication, effectively control mood swings, enhance disease self-management and social functions, decrease the risks of relapse and re-hospitalization, and stabilize overall health. The present article firstly introduces the characteristics and etiological assumptions related to BD, the related evidence-based care models and their effects, and the early development of an evidence-based care model, the BalancingMySwing group, for BD patients in Taiwan. This article provides updated information to clinicians who are involved in caring for this population. Moreover, the existing data related to biological and psychosocial factors for BD in Taiwan is insufficient and developing individual-tailored psychosocial intervention is urgently needed. The authors hope that this article will elicit greater concern for this issue from policy decision-makers and healthcare providers.雙相情緒障礙症病患之照護.雙相情緒障礙症（簡稱雙相症）為具有慢性化、高度復發性及不穩定性，及高自殺率之嚴重精神疾病。實證研究支持遺傳及基因因素、神經發炎反應與社會節奏失衡，彼此之間惡性循環為其重要病因。因此，雙相症的急性期照護應以藥物治療為主，後續維持期則需合併藥物治療及心理社會治療，方能有效協助該族群病患規則服藥及處理情緒起伏症狀，促進其疾病自我管理及社會功能，終而降低復發及再住院，並達到較佳穩定狀態。本文首先介紹雙相症之疾病特性、病因假說、實證照護模式與成效，再以「盪鞦韆團體」為例，簡介國人雙相症實證照護模式的初步發展。期藉由這些實證照護知識的統整與分享，做為臨床工作者照護此族群病患的參考，更且，由於目前探討國人雙相症心理社會相關因素之研究仍十分欠缺，發展該族群病患合適的心理社會治療模式亦刻不容緩，盼望藉由本文拋磚引玉，以引發相關決策單位與健康照護者對於此臨床問題的關切。.

Peptidylarginine deiminase type 2 (PADI2) deiminates (or citrullinates) arginine residues in protein to citrulline residues in a Ca2+-dependent manner, and is found in lymphocytes and macrophages. Vimentin is an intermediate filament protein and a well-known substrate of PADI2. Citrullinated vimentin is found in ionomycin-induced macrophage apoptosis. Citrullinated vimentin is the target of anti-Sa antibodies, which are specific to rheumatoid arthritis, and play a critical role in the pathogenesis of the disease. To investigate the role of PADI2 in apoptosis, we generated a Jurkat cell line that overexpressed the PADI2 transgene from a tetracycline-inducible promoter, and used a combination of 12-O-tetradecanoylphorbol-13-acetate and ionomycin to activate Jurkat cells. We found that PADI2 overexpression reduced the cell viability of activated Jurkat cells in a dose- and time-dependent manner. The PADI2-overexpressed and -activated Jurkat cells presented typical manifestations of apoptosis, and exhibited greater levels of citrullinated proteins, including citrullinated vimentin. Vimentin overexpression rescued a portion of the cells from apoptosis. In conclusion, PADI2 overexpression induces apoptosis in activated Jurkat cells. Vimentin is involved in PADI2-induced apoptosis. Moreover, PADI2-overexpressed Jurkat cells secreted greater levels of vimentin after activation, and expressed more vimentin on their cell surfaces when undergoing apoptosis. Through artificially highlighting PADI2 and vimentin, we demonstrated that PADI2 and vimentin participate in the apoptotic mechanisms of activated T lymphocytes. The secretion and surface expression of vimentin are possible ways of autoantigen presentation to the immune system.

e14638 Background: Breast cancer is the highest incidence malignancies in women worldwide. Luminal breast cancers are typically estrogen receptor–positive with better prognosis. However, the rapid disease progression and the high relapse rate of this subtype of breast cancer have become a puzzle in breast cancer treatment. It gave us the motivation to figure out the anomalous molecular mechanism which devoted in. It has been well-documented that the RAS pathway is overloadly activated in more than half of human breast tumors. RAS genes encode a superfamily of small GTPases that contribute to cell growth signals. Methods: Gene expression level were measured by qPCR and Western Blot.Biological effects of each condition were evaluated in cell viability and migration. Results: In this study, we investigated one member of the RAS family, RERG, which was related to the ER pathway and contributed to inhibit Ras activated pathway. Our results showed that knockdown of RERG concomitantly promoted two major oncogenic pathways, Ras and Stat3 signaling pathways, in luminal type breast cancer cell lines. Moreover, ectopic RERG expression significantly inhibited Ras expression. It implicated that RERG mediated in RAS-driven biological effects. Our findings indicated that knockdown of RERG enhanced mobility of the breast cancer cells and made cells more intractable under SERM treatment. Conclusions: We elucidated the tumor-suppressor role of RERG in breast cancer cells though inhibition of the Ras and Stat3 signaling pathways. Therefore, this study might shed light on the important mechanistic insight into the tumorigenesis of ER-positive luminal type cancer and provided the prognostic and therapeutic improved roles of RERG.

Cell therapy is a promising strategy for the treatment of human diseases. While the first use of cells for therapeutic purposes can be traced to the 19th century, there has been a lack of general and reliable methods to study the biodistribution and associated pharmacokinetics of transplanted cells in various animal models for preclinical evaluation. Here, we present a new platform using albumin-conjugated fluorescent nanodiamonds (FNDs) as biocompatible and photostable labels for quantitative tracking of human placenta choriodecidual membrane-derived mesenchymal stem cells (pcMSCs) in miniature pigs by magnetic modulation. With this background-free detection technique and time-gated fluorescence imaging, we have been able to precisely determine the numbers as well as positions of the transplanted FND-labeled pcMSCs in organs and tissues of the miniature pigs after intravenous administration. The method is applicable to single-cell imaging and quantitative tracking of human stem/progenitor cells in rodents and other animal models as well.

This pilot study tested the feasibility and receptivity of a family psychoeducation protocol for Chinese-American adult schizophrenic patients and their caregivers. Although family psychoeducation had been proven a robust intervention, little empirical evidence is available on minority groups in the United States. This ethnically sensitive treatment adapted to Chinese immigrants had a shorter 6-month treatment and involved both multifamily group for caregivers and single-family group for individual families. Twelve families were recruited, nine in the intervention group and three in the comparison group. Four waves of data were collected at baseline, 3-month, termination, and 3-month follow-up. Most changes in outcome measures at termination and follow-up for the intervention group compared to baseline and relative to the comparison group were in the expected direction. Patient symptomatology and quality of life, and caregiver knowledge of the illness, treatment and community resources, and social support...

Peptidylarginine deiminase IV (PADI4) posttranslationally converts peptidylarginine to citrulline. It plays an essential role in immune cell differentiation and apoptosis. A haplotype of single-nucleotide polymorphisms (SNPs) in PADI4 is functionally relevant as a rheumatoid arthritis (RA) gene. It could increase enzyme activity leading to raised levels of citrullinated protein and stimulating autoantibody. Previously, our study showed that inducible PADI4 causes haematopoietic cell death. Herein, we further investigate whether RA risk PADI4 haplotype (SNP PADI4; S55G, A82V and A112G) and the increase of its enzymatic activity induce apoptosis. In the tetracycline (Tet)-On Jurkat T cells, ionomycin (Ion) only treatment didn't induce apoptosis however it promoted inducible PADI4-decreased cell viability and -enhanced apoptosis. Through in vitro and in vivo PADI enzyme activity assay, we demonstrated that PADI4 enzyme activity of SNP PADI4 was higher than RA non-risk PADI4 haplotype (WT PADI4). The effect of SNP PADI4-induced apoptosis was superior to WT PADI4. In addition, both Ion and SNP PADI4 synergistically provoked apoptosis were compared with both Ion and WT PADI4. Concurrently, in the conditionally inducible SNP PADI4 cells of Ion treatment-induced apoptosis, not only the expression of Bcl-xL was down-regulated and Bax up-regulated, but also cytochrome c was released from mitochondria to cytoplasm in significant amounts. Western blotting data showed the increase in apoptosomal caspase activation during programmed cell death in the inducible SNP PADI4 cells subsequent to Ion treatment. These data demonstrated that both SNP PADI4 increasing their enzyme activity could enhance apoptosis through the mitochondrial pathway and further provide a conceivable explanation in the pathogenesis of RA following the upregulation of PADI4 activity in its SNPs.

Flap endonuclease 1 (FEN1) is one of the most important proteins in maintaining genome stability and preventing carcinogenesis. In recent years, the contribution of two variants of FEN1, rs174538 and rs4246215, regarding cancer risk have been investigated in lung, breast, liver, esophageal, gastric, colorectal cancer and glioma. However, it has not been revealed whether rs174538 and rs4246215 are associated with leukemia. Therefore, in the present study we aimed to evaluate the contribution of these genotypic polymorphisms in FEN1 to childhood acute lymphoblastic leukemia (ALL) risk in Taiwan.In total, 266 patients with childhood ALL and an equal number of recruited non-cancer controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).The FEN1 rs174538 genotype, but not rs4246215, was differently distributed between childhood ALL and control groups. The AG and AA of FEN1 rs174538 genotypes were significantly less frequently found in childhood ALL patients than in controls (odds ratio [OR]=0.68 and 0.48, 95%confidence intervals [CI]=0.47-0.98 and 0.24-0.82, respectively). As for gender, boys carrying the FEN1 rs174538 AG or AA genotype conferred lower ORs of 0.55 and 0.36 (95%CI=0.33-0.91 and 0.18-0.73, p=0.0053) for childhood ALL. Regarding age, those equal to or greater than 3.5 years of age at onset carrying the FEN1 rs174538 AG or AA genotype were of lower risk (ORs=0.53 and 0.32, 95%CI=0.31-0.90 and 0.15-0.70, p=0.0042).The FEN1 rs174538 A allele is a protective biomarker for childhood ALL and this association is more significant in males and in patients at onset age of 3.5 years or older.

Lung cancer is the leading cause of cancer-related death worldwide. Interleukin-4 (IL-4) is a typical pleiotropic T helper 2 cytokine involved in immunology during carcinogenesis. The present study aimed at evaluating the contribution of IL-4 promoter T-1099G (rs2243248), C-589T (rs2243250), C-33T (rs2070874) genetic polymorphisms to the risk of lung cancer in Taiwan.The contributions of the promoter IL-4 polymorphic genotypes to lung cancer risk were investigated in 358 lung cancer patients and 716 age- and gender-matched healthy controls. In addition, the interaction between IL-4 and individual smoking status was also evaluated.The percentages of CC, CT and TT for IL-4 C-589T genotypes were differentially represented as 69.0%, 26.5% and 4.5% in the lung-cancer patient group and 61.3%, 30.4% and 8.3% in the non-cancer control group, respectively (p=0.0156). The TT genotype carriers were of lower risk for lung cancer (odds ratio (OR)=0.48, 95% confidence interval (CI)=0.27-0.86, p=0.0106) than the CC genotype carriers. We also analyzed the allelic frequency distributions and the results showed that the T allele of IL-4 C-589T conducted a protective effect on lung cancer susceptibility (p=0.0022). On the contrary, there was no difference in the distribution of genotypic or allelic frequencies among patients and controls for the IL-4 promoter T-1099G and C-33T.The TT genotype of IL-4 C-589T compared to the CC wild-type genotype may have a protective effect on lung cancer risk in Taiwan and may serve as an early detection and prediction marker.

Two studies using the Parent—Adult Attachment Style Questionnaire (P—AASQ) are described. In both, college students were classified into 1 of 3 parent—adult attachment style groups, and their score...

Public attitudes toward mental illness influence the success with which patients reenter the community. An attitude instrument suitable to the Chinese cultural setting with good reliability and validity is essential to examining public attitudes toward mental illness. Exploring the perspectives of adolescents is relevant because most mental illness occurs during adolescence.This study developed and tested the psychometric quality of the Chinese-version Attitudes Toward Mental Illness (CAMI) scale among senior high school students.The original AMI was translated into Chinese using a back and forth translation method and its content validity was examined. A cross-sectional survey of 479 senior high school students was conducted to assess the construct validity, cross validity, and internal consistency of the CAMI.The CAMI showed adequate content validity. The confirmatory factor analysis support: the appropriateness of CAMI's original two-factor structure of negative attitude and recovery outcomes after deleting items 9 and 11; the measurement of the negative perceptions of mentally ill patients and their risks to community; and the perceptions of recovery of mentally ill patients. The construct validity and cross validity are appropriate and the internal consistency of the total scale and two subscales are acceptable (Cronbach's α: .76, .75, .81).The reliability and validity of the CAMI is appropriate for the sample of senior high students in this study. Future studies should target a broader range of people in order to establish the reliability and validity of the scale in different groups and to build up empirical knowledge on public attitudes toward mental illness. The application of this scale is expected to contribute to the development of anti-stigma interventions and to the creation of friendly communities for mentally ill patients.中文版精神疾病態度量表之信效度研究—以高中生為例民眾對精神疾病的態度將影響精神病患回歸社區。發展適於華人社會且信、效度良好的測量工具，有助於瞭解民眾對於精神疾病之觀感，且由於精神疾病好發於青少年階段，該族群對於精神疾病之看法值得進一步探究。以高中生為例，發展及測試中文版精神疾病態度量表之信、效度。運用來回翻譯法將精神疾病態度量表中文化，並建立內容效度；再採橫斷面研究設計，以479位高中生為樣本進行問卷調查，評估量表之建構效度、複核效度及內在一致性信度。中文版精神疾病態度量表內容效度良好，依據驗證性因素分析刪除第9和11題後，顯示中文版量表支持原量表之兩因素結構：負向態度及復元成效，具有適當之建構效度及複核效度，且總量表及兩次量表之內在一致性信度達可接受範圍（Cronbach’s α分別為.76、.75、.81）。中文版精神疾病態度量表於高中生樣本測試所得信、效度適當，未來宜進一步以成人民眾為對象，建立於不同族群及年齡層之信、效度，藉此可瞭解國人對精神病患的觀感，並發展合宜的介入策略，以建構對精神病友較為友善的社區環境。

Ornithine decarboxylase (ODC), the key enzyme of polyamine biosynthesis, has paradoxical roles in apoptosis. Our published papers show overexpression of ODC prevents the apoptosis induced by many cytotoxic drugs. Thapsigargin (TG) is an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca(2+) ATPase (SERCA) pumps and causes ER stress-induced apoptosis. We used ODC overexpressing cell lines to examine whether overexpression of ODC inhibits TG-induced apoptosis. Our results indicated overexpression of ODC attenuated TG-induced apoptosis. Overexpression of ODC blocked procaspase-4 cleavage and phosphorylation of protein kinase-like ER-resident kinase (PERK), triggered by TG. It also attenuated the increase in CAAT/enhancer binding protein homologous protein (CHOP). Cells with overexpressed ODC had greater Bcl-2 expression. Overexpression of ODC preserved the expression of Bcl-2, inhibited the increase in Bak and stabilized mitochondrial membrane potential without the influences of TG. Cytochrome c release and down-stream caspase activation were blocked. That is, overexpression of ODC inhibits the mitochondria-mediated apoptotic pathway, induced by TG. Finally, overexpression of ODC maintains the protein and mRNA expression of SERCA. In conclusion, overexpression of ODC suppresses TG-induced apoptosis by blocking caspase-4 activation and PERK phosphorylation, attenuating CHOP expression and inhibiting the mitochondria-mediated apoptotic pathway.

Ornithine decarboxylase (ODC), a tumor promoter, provokes cell proliferation, and inhibits cell death; but the mechanism involved in cell differentiation remains unknown. Herein, we examine whether it functions during macrophage-like differentiation. Previous studies reveal that ODC, a rate-limiting enzyme of polyamine biosynthesis, and polyamines are involved in restraining immune response in activated macrophage. By using 12-O-tetradecanoylphorbol-13-acetate (TPA)-differentiated human promyelocytic HL-60 and promonocytic U-937 cells, we discover that polyamines block the expression, secretion and activation of MMP-9. Meanwhile conventional expression of ODC represses tumor necrosis factor-alpha (TNF-alpha) expression and nuclear factor-kappaB (NF-kappaB) activation as well as MMP-9 enzyme activity. Following stimulation by TNF-alpha, the secretion of MMP-9 is restored in ODC-overexpressed cells. In addition, the NF-kappaB inhibitors (pyrrolidinedithiocarbamate, BAY-11-7082 and lactacystin) suppress the TPA-induced MMP-9 enzyme activity. Concurrently, both the irreversible inhibitor of ODC, alpha-difluoromethylornithine, and TNF-alpha could not recover MMP-9 activation following NF-kappaB inhibitor treatment in parental cells. Furthermore, ODC could directly inhibit and attenuate NF-kappaB DNA binding and transcriptional activation. Therefore, we suggest that ODC inhibits the TNF-alpha-elevated MMP-9 activation via NF-kappaB as TPA-induced macrophage-like differentiation and this interrupting mechanism may provide a new conceivable resolution why leukemia is poorly differentiated besides atypical growth.

Curcumin, a well-known dietary pigment derived from the food flavoring turmeric (Curcuma longa) exhibits anti-proliferative, anti-inflammatory, and anti-oxidative activities. Recently, studies have shown that a chemopreventive effect of curcumin could be due to the hyperproduction of reactive oxygen species (ROS) inducing apoptosis in tumor cells. In our previous studies, ornithine decarboxylase (ODC) overexpression prevented tumor necrosis factor alpha (TNF-alpha)- and methotrexate-induced apoptosis via reduction of ROS. Furthermore, ODC is the rate-limiting enzyme in polyamine biosynthesis and a target for chemoprevention. In this study, we found that enzyme activity and protein expression of ODC were reduced during curcumin treatment. Overexpression of ODC in human promyelocytic leukemia HL-60 parental cells could reduce curcumin-induced apoptosis, which leads to loss of mitochondrial membrane potential (Deltapsi(m)), through reducing intracellular ROS. Moreover, ODC overexpression prevented cytochrome c release and the activation of caspase-9 and caspase-3 following curcumin treatment. These results demonstrate that curcumin-induced apoptosis occurs through a mechanism of down-regulating ODC and along a ROS-dependent mitochondria-mediated pathway.

Antizymes delicately regulate ornithine decarboxylase (ODC) enzyme activity and polyamine transportation. One member of the family, antizyme-1, plays vital roles in molecular and cellular functions, including developmental regulation, cell cycle, proliferation, cell death, differentiation and tumorigenesis. However, the question of how does it participate in the cell apoptotic mechanism is still unsolved. To elucidate the contribution of human antizyme-1 in haematopoietic cell death, we examine whether inducible overexpression of antizyme enhances apoptotic cell death. Antizyme reduced the viability in a dose- and time-dependent manner of human leukemia HL-60 cells, acute T leukemia Jurkat cells and mouse macrophage RAW 264.7 cells. The apoptosis-inducing activities were determined by nuclear condensation, DNA fragmentation, sub-G(1) appearance, loss of mitochondrial membrane potential (Deltapsi( m )), release of mitochondrial cytochrome c into cytoplasm and proteolytic activation of caspase 9 and 3. Following conditional antizyme overexpression, all protein levels of cyclin-dependent kinases (Cdks) and cyclins are not significantly reduced, except cyclin D, before their entrance into apoptotic cell death. However, introduced cyclin D1 into Jurkat T tetracycline (Tet)-On cell system still couldn't rescue cells from apoptosis. Antizyme doesn't influence the expression of tumor suppressor p53 and its downstream p21, but it interferes in the expressions of Bcl-2 family. Inducible antizyme largely enters mitochondria resulting in cytochrome c release from mitochondria to cytosol following Bcl-xL decrease and Bax increase. According to these data, we suggest that antizyme induces apoptosis mainly through mitochondria-mediated and cell cycle-independent pathway. Furthermore, antizyme induces apoptosis not only by Bax accumulation reducing the function of the Bcl-2 family, destroying the Deltapsi( m ), and releasing cytochrome c to cytoplasm but also by the activation of apoptosomal caspase cascade.

Methotrexate pneumonitis is an unpredictable and life-threatening side effect of methotrexate therapy. Early diagnosis, cessation of methotrexate, and treatment with corticosteroids and/or cyclophosphamide are important in the management of patients with methotrexate pneumonitis. Methotrexate pneumonitis has not been reported in patients of Chinese ethnicity. We report a case of methotrexate pneumonitis in a Taiwan patient with rheumatoid arthritis who presented with acute nonproductive cough, dyspnea, fever, severe hypoxemia, and rapid progression to respiratory failure. Chest roentgenogram demonstrated bilateral diffuse interstitial and alveolar infiltration. Thoracoscopic biopsy with wedge resection of the upper lobe of the right lung was performed and the histologic findings of the biopsy specimen were consistent with bronchiolitis obliterans with organizing pneumonia. Rapid improvement of methotrexate pneumonitis was achieved after pulse therapies of methylprednisolone and cyclophosphamide and daily use of prednisolone.