Death education for undergraduate nursing students in the China Midwest region: An exploratory analysis.

AIM: The purpose of this study was to comprehend the need for incorporating death education within the curriculum of undergraduate nursing students and to assess the factors that impact the desire for such education. DESIGN: We enlisted undergraduate nursing students from several nursing colleges located in the central and west region of China. Undergraduate students who fulfilled the eligibility criteria between January and February 2021 were chosen to participate. Data were collected via an online platform called Questionnaire Star. The survey encompassed a general information questionnaire and a scale for assessing the need for education on the topic of death. Descriptive statistical analysis was performed using the SPSS 20.0 software, while multivariate stepwise regression was employed for more complex analysis. Statistical significance was indicated when the p-value was below 0.05, and high statistical significance was noted when the p-value fell below 0.01. METHODS: We designed a descriptive quantitative approach to investigate the need for death education and its associated factors. The research involved 907 undergraduate nursing students from the central and west region of China. The data collection was done through the Questionnaire Star platform. RESULTS: Following the collection of completed surveys, individuals displaying contradictory responses were omitted. Out of 911 surveys disseminated, 907 were successfully collected, resulting in a recovery rate of 99.6%. Among the participants, 769 identified as female, constituting 84.8% of the total, while 138 identified as male, making up 15.2%. The survey findings indicated that factors such as residency, parental educational history and exposure to hospice care education significantly impacted the need for death education among undergraduate nurses (p < 0.05). CONCLUSIONS: Among students pursuing a nursing degree at the undergraduate level, there was a pronounced need for education related to the topic of death. Offering such education to these students is essential, as it helps cultivate a proper understanding of death. This, in turn, contributes to enhancing the overall quality of patient care throughout their life journey. PATIENT OR PUBLIC CONTRIBUTION: A total of 907 nursing undergraduates from central and western China participated in the questionnaire.

An Inpatient Psychiatric Program Targeting Opioid Overdoses.

The United States is currently experiencing an opioid epidemic, as drug overdose deaths have become a leading cause of death. According to the Centers for Disease Control, in 2017, opioids were responsible for 47,000 deaths, which involved both illicit and prescription opioids. A multifaceted public health approach that utilizes public health authorities, health care providers, local hospitals, and affected communities is required to effectively reduce opioid-related morbidity and mortality. The authors of this paper developed an inpatient program on the dual-diagnosis unit at Gracie Square Psychiatric Hospital in New York to target the opioid crisis. The purpose of this program was to train patients and their families on how to respond to an opioid overdose and administer naloxone spray. The paper describes the implementation of this program.

Recent advances in the discovery and development of Ebola virus inhibitors / 药学学报

Ebola virus is extremely virulent and highly contagious. Ebola virus causes outbreaks of severe hemorrhagic fever, with human mortality rates of up to 90%. There is currently no preventive or therapeutic treatment in the form of vaccines, biological or small molecular agents. Currently, a lot of anti-Ebola virus agents have been reported. Here, we review the latest advances in this field.

Advances in research on HBV inhibitors based on new targets (2): RNase H and others / 药学学报

Hepatitis B has become one of the major diseases which seriously affect people's health and social development. Hepatitis B, with high incidence and long disease course, cannot be cured by approved drugs such as the nucleoside analogues. Therefore, the discovery of safe and efficient novel HBV inhibitors is of great significance. From the point of view of medicinal chemistry, we summarized and discussed current endeavours towards the discovery and development of anti-HBV agents of RNase H and other novel target inhibitors with various scaffolds or distinct mechanisms of action, besides the existing capsid protein inhibitors.

Advances in research on HBV inhibitors based on new targets (1): capsid protein inhibitors / 药学学报

Hepatitis B virus (HBV) capsid protein plays an important role in the life cycle, thus becoming an ideal target for drug design. Capsid protein inhibitors can exert a synergistic antiviral effect with nucleoside drugs by inhibiting the replication of HBV. This paper reviews the research progress of capsid protein inhibitors with different structural types from the perspective of medicinal chemistry.

Effects of Kinesio Taping Combined with Deep Muscle Stimulation on Non-specific Neck Pain / 中国康复理论与实践

Objective:To investigate the clinical effects of Kinesio Taping (KT) combined with deep muscle stimulation (DMS) on non-specific neck pain (NNP). Methods:From January to December, 2018, 56 patients with NNP were randomly divided into control group (n = 28) and study group (n = 28). The control group accepted interference electrotherapy and magnetic vibration heat, and the study group accepted KT and DMS in addition, for two weeks. They were assessed with Visual Analogue Scale (VAS) of pain and Neck Disability Index (NDI) before treatment, and after one and two weeks of treatment. Results:The score of VAS and NDI decreased after treatment (F > 4.137, P < 0.05), and were less in the study group than in the control group (t > 4.008, P < 0.001). Conclusion:KT combined with DMS could promote the relief of NNP.

Association Between the Communication Skills of Physicians and the Signing of Do-Not-Resuscitate Consent for Terminally Ill Patients in Emergency Rooms (Cross-Sectional Study).

BACKGROUND: The signing of do-not-resuscitate (DNR) consent is mandatory in providing a palliative approach in the end-of-life care for the terminally ill patients and requires an effective communication between the physician and the patients or their family members. This study aimed to investigate the association between the communication skills of physicians who participated in the SHARE (supportive environment, how to deliver the bad news, additional information, reassurance, and emotional support) model course on the patient notification and the signing of do-not-resuscitate (DNR) consent by the terminally ill patients at emergency rooms. METHODS: Between May 1, 2017 and April 30, 2018, a total of 109 terminally ill patients were enrolled in this study, of which 70 had signed a DNR and 39 had not. Data regarding the patients' medical records, a questionnaire survey completed by family members, and patient observation forms were used for the assessment of physicians' communication skills during patient notification. The observation form was designed based on the SHARE model. A multivariate logistic regression model was applied to identify the independent significant factors of the patient and family member variables as well as the four main components of the observation form. RESULTS: The results revealed that knowing how to convey bad news and providing reassurance and emotional support were significantly correlated with a higher rate of signing DNR consent. Additionally, physician-initiated discussion with family members and a predicted limited life expectancy were negative independent significant factors for signing DNR consent. CONCLUSION: This study revealed that good communication skills help to increase the signing of DNR consent. The learning of such skills from attendance of the SHARE model course is encouraged for the physicians in the palliative care of terminally ill patients in an emergency room.

The training in SHARE communication course by physicians increases the signing of do-not-resuscitate orders for critical patients in the emergency room (cross-sectional study).

BACKGROUND: Communication skills may be an important skill for the front-line emergency physicians. AIM: This study aimed to investigate the effect of training in a SHARE communication course by emergency physicians on patient notification and signing of do-not-resuscitate (DNR) orders for critical patients in the emergency room. DESIGN: From a total of 29 attending physicians in the emergency department, 19 physicians had been trained in the SHARE communication course. An observation form designed based on the SHARE training was completed by two observers who noted the communication process between physicians and patients and family members during patient notification and signing a DNR order. To assess the influence of physicians trained in a SHARE communication course on the signing of DNR orders, a propensity score-matched population was created to reduce the potential selection bias of patients and family members. SETTING: Level 1 trauma medical center in southern Taiwan. RESULTS: There were 145 individuals enrolled in the study, of which 93 signed the DNR order, and 52 did not sign it. Analysis from 23 matched pairs from this population revealed that significantly more family members would sign a DNR order if the physician had been trained in the SHARE communication course than when they did not receive this training (78.3% vs. 39.1%, respectively, p = 0.017). The overall score of the observation form for physicians was higher in those individuals who had signed a DNR order than in those who did not sign it (29.48 ±â€¯3.72 vs. 26.13 ±â€¯3.52, respectively, p = 0.003), especially when the physician had chosen a quiet environment (1.35 ±â€¯0.65 vs. 0.87 ±â€¯0.69, respectively, p = 0.020), understood the patient's wishes and confirmed them (1.78 ±â€¯0.42 vs. 1.30 ±â€¯0.70, respectively, p = 0.008), and expressed concern (1.48 ±â€¯0.79 vs. 0.96 ±â€¯0.77, respectively, p = 0.028). In addition, a feedback survey about the feelings experienced by these physicians during the process of patient notification did not reveal a significant difference during the communication with those who had or had not signed DNR orders. CONCLUSION: The training in a SHARE communication course can improve the communication skills of emergency physicians in patient notification and signing of DNR orders for critical patients.

Induction chemotherapy followed by concurrent chemoradiation and nimotuzumab for locoregionally advanced nasopharyngeal carcinoma: preliminary results from a phase II clinical trial.

Overexpression of epidermal growth factor receptor can be found in more than 80% of patients with locoregionally advanced nasopharyngeal carcinoma and is associated with shorter survival. In this work, we evaluated the feasibility of adding nimotuzumab to chemoradiation in locoregionally advanced nasopharyngeal carcinoma. Twenty-three patients with clinically staged T3-4 or any node-positive disease were enrolled. They were scheduled to receive one cycle of induction chemotherapy followed by intensity-modulated radiotherapy, weekly administration of nimotuzumab and concurrent chemotherapy. Results showed that all patients received a full course of radiotherapy, 19(82.6%)patients completed the scheduled neoadjuvant and concurrent chemotherapy, and 22(95.7%) patients received ≥6 weeks of nimotuzumab. During the period of concurrent chemoradiation and nimotuzumab, grade 3-4 toxicities occurred in 14(60.9%) patients: 8 (34.8%) had grade 3-4 oral mucositis, 6(26.1%) had grade 3 neutropenia, and 1(4.3%) had grade 3 dermatitis. No acne-like rash was observed. With a median follow-up of 24.1 months, the 2-year progression-free survival and overall survival were 83.5% and 95.0%, respectively. In conclusion, concurrent administration of chemoradiation and nimotuzumab was well-tolerated with good compliance. Preliminary clinical outcome data appear encouraging with favorable normal tissue toxicity results comparing with historical data of concurrent chemoradiation plus cetuximab.

The expression and effect of LINGO-1 during the differentiation of spinal cord derived neural stem cells / 中国组织工程研究

BACKGROUND: It is of great significance to explore the expression and effect of LINGO-1 in the differentiation of spinal cord derived neural stem cells (SpNSCs) for regulating neural stem cell differentiation and repairing spinal cord injury. OBJECTIVE: To investigate the expression features and biological effects of LINGO-1 in the differentiation of SpNSCs. METHODS: SpNSCs were isolated from the rat spinal cord and cultured in vitro. The expression characteristics of LINGO-1 was observed through double immunofluorescence staining of LINGO-1 and Nestin (neural stem cells), β-Tubulin III (neurons), GFAP (astrocytes) and O4 (oligodendrocyte) at 0-5 days of differentiation. SpNSCs isolated from the rat spinal cord were cultured in vitro and divided into siRNA group and control group. The siRNA group was transfected with LINGO-1 shRNA lentiviral vector to down-regulate the expression of LINGO-1, and the control group was transfected with Scramble-shRNA lentiviral vector. The growth of neurites was detected by immunofluorescence staining at 5 days after transfection.RESULTS AND CONCLUSION: The SpNSCs could differentiate into neurons, astrocytes and oligodendrocytes. LINGO-1 was expressed in SpNSCs, neurons and oligodendrocytes, but not in astrocytes. The neurite length of the siRNA group was significantly longer than that of the control group (P < 0.05). In summary, the SpNSCs have the potential of multi-directional differentiation, and LINGO-1 has a negative effect on the neurite growth.

[The Effects of a Mobile Application Social Support Program on Postpartum Perceived Stress and Depression].

BACKGROUND: Postpartum depression is a common health problem for women following childbirth. Using effective social support to reduce postpartum depression has become an important issue. The current popularity of smartphones offers new possibilities for interventional methods. PURPOSE: To investigate the effects of mobile-application-based social support programs on perceived stress and postpartum depression in postpartum women. METHODS: The present study employs an experimental research design. 126 smartphone users at 36 weeks' gestation were assigned randomly to the intervention (n = 61) or the control (n = 65) group. The intervention group received a social-support intervention via the mobile application Line twice per week for a period of 4 weeks after childbirth. The control group did not receive the intervention. The Perceived Stress Scale-Chinese version and Edinburg Postnatal Depression Scale were used to evaluate the outcome. RESULTS: Participants in the intervention group had significantly lower perceived stress (F = 27.25, p < .001) and postpartum depression (F = 35.73, p < .001) than their control group peers. CONCLUSIONS: Social-support programs that are delivered via mobile applications such as Line may significantly reduce the perceived stress and postpartum depression of women during the early postpartum period. The results support the implementation of mobile-application-based social support programs in postpartum care.

A scoping review of medical professionalism research published in the Chinese language.

BACKGROUND: The Chinese Medical Doctors Association (CMDA) adopted the Charter of Medical Professionalism in the New Millennium (Charter) and published the Chinese Medical Doctor Declaration (Declaration). This is an important step to re-building medical professionalism in China at a time when the commercialization of health care has led to a decline in physician accountability and public trust in the profession. In response, authors have begun to examine and promote medical professionalism in China. This study aims to present the key research themes, identify research gaps and offer recommendations from reviewing the increasing pool of Chinese-language literature on medical professionalism. METHODS: A scoping review of Chinese language papers was conducted using the China National Knowledge Infrastructure (including China Academic Journals Full-text Database, China Doctoral Dissertations Full-text Database, Masters' Theses Full-text Database, China Core Newspapers Full-text Database, and China Yearbooks Full-text Database) (CNKI) database. RESULTS: Four major research themes were identified in Chinese discourse: (1) teaching professionalism, (2) practicing professionalism, (3) conceptualizing professionalism and (4) assessing professionalism. Overall, authors were concerned with the cultivation of humanism in physicians and emphasized the importance of communication skills to improve the physician-patient relationship in China. They explored the role of traditional Chinese values, such as Confucian and Taoist values, as well as the Communist Party's political values, in promoting professional behaviour. CONCLUSIONS: Authors demonstrate increasing interest in medical professionalism in China. The literature is of variable quality and further empirical studies are required in order to evaluate teaching interventions and guide professionalism assessment. A common professionalism framework is absent and could be developed with consideration to China's socio-cultural context.

Effects of Resourcefulness on Sleep Disturbances, Anxiety, and Depressive symptoms in Family Members of Intensive Care Unit Patients.

The study aimed to investigate the relationships among psychological distresses, resourcefulness, sleep disturbances, anxiety and depressive symptoms in family members of intensive care unit (ICU) patients. A cross-sectional, descriptive correlational design was employed. Using structural equation modeling (SEM) approach, relationships among factors, mediators, and outcomes were analyzed. The SEM explained 59% of the variances in depressive symptoms and 36% in anxiety. Family members with greater learned resourcefulness had fewer sleep disturbances, depressive and anxiety symptoms. Nursing professionals need to detect psychiatric disease of family members and must be especially vigilant with people who have low resourcefulness and sleep disturbances.

Krüppel-Like Factor 5 Promotes Epithelial Proliferation and DNA Damage Repair in the Intestine of Irradiated Mice.

BACKGROUND & AIMS: High doses of radiation induce severe DNA damage in intestinal epithelial cells, especially crypt cells, and cause intestinal injury, but the underlying molecular mechanisms remain unclear. Krüppel-like factor 5 (KLF5), a zinc finger-containing transcription factor, is induced by various stress stimuli and is involved in cell proliferation and survival. The role of KLF5 in radiation-induced intestinal injury was investigated here. METHODS: Wild type mice were treated with 8 or 15 Gy total body irradiation (TBI). KLF5 content and cellular localization in the small intestines of irradiated mice were detected by Western blot and immunohistochemical analysis. Mice with intestinal-specific knockdown of KLF5 (Vil-Cre; Klf5(fl/+) mice) were generated and their response to radiation was compared with controls. Morphological changes were determined by hematoxylin and eosin staining. Proliferation was examined by Ki67 immunostaining. The molecular response of the small intestine after KLF5 knockdown was investigated using microarrays. RESULTS: KLF5 expression correlated with the progression of intestinal damage. Decreased levels of KLF5 in the gut were associated with increased damage to the intestinal mucosa and reduced epithelial proliferation after TBI. Our microarray data disclosed that KLF5 knockdown down-regulated genes related to DNA damage repair pathways such as nucleotide excision repair, mismatch repair, non-homologous end joining and the Fanconi anemia pathway, which may suggest a novel function of KLF5. CONCLUSIONS: Our study illustrates that KLF5 may modulate DNA repair pathways to prevent intestinal injury induced by TBI. KLF5 signaling provides a novel field for identification of potential therapeutic targets for the treatment of radiation-induced intestinal damage.

The relationship between survival after out-of-hospital cardiac arrest and process measures for emergency medical service ambulance team performance.

OBJECTIVE: International institutes have developed their own clinical performance indicators for ambulance services. It is unknown whether these process measures are related to survival of patients after out-of-hospital cardiac arrest (OHCA). We aimed to determine whether Emergency Medical Service (EMS)-related ambulance team process measures correlate with patient survival. METHODS: Four years of observational data were collected from an urban EMS OHCA registry. The two process measures were achieving an EMS response time ≤4 min and prehospital ROSC (return of spontaneous circulation). The outcome measure was survival to discharge. We used the GLMM (generalised linear mixed model) with stepwise selection to examine this process-outcome link at the patient and EMS team levels, respectively. RESULTS: We analyzed 3856 OHCA patients distributed across forty-three EMS ambulance teams. Survival to discharge was observed in 193 (5%) patients. The two EMS team process measures were positively associated with an improvement in survival at the patient level after case-mix adjustment. However, they were not associated with improvement in the risk-adjusted survival rate. CONCLUSIONS: The EMS team-level process measures proposed by international institutes may not predict the risk-adjusted survival rate. Using these measures to motivate EMS teams to improve their quality performance would be questionable. Increased efforts should be devoted to constructing more pivotal EMS team-level process measures that are tightly linked to survival.

Biological effects of low-dose-rate irradiation of pancreatic carcinoma cells in vitro using 125I seeds.

AIM: To determine the mechanism of the radiation-induced biological effects of 125I seeds on pancreatic carcinoma cells in vitro. METHODS: SW1990 and PANC-1 pancreatic cancer cell lines were cultured in DMEM in a suitable environment. Gray's model of iodine-125 (125I) seed irradiation was used. In vitro, exponential phase SW1990, and PANC-1 cells were exposed to 0, 2, 4, 6, and 8 Gy using 125I radioactive seeds, with an initial dose rate of 12.13 cGy/h. A clonogenic survival experiment was performed to observe the ability of the cells to maintain their clonogenic capacity and to form colonies. Cell-cycle and apoptosis analyses were conducted to detect the apoptosis percentage in the SW1990 and PANC-1 cells. DNA synthesis was measured via a tritiated thymidine (3H-TdR) incorporation experiment. After continuous low-dose-rate irradiation with 125I radioactive seeds, the survival fractions at 2 Gy (SF2), percentage apoptosis, and cell cycle phases of the SW1990 and PANC-1 pancreatic cancer cell lines were calculated and compared. RESULTS: The survival fractions of the PANC-1 and SW1990 cells irradiated with 125I seeds decreased exponentially as the dose increased. No significant difference in SF2 was observed between SW1990 and PANC-1 cells (0.766±0.063 vs 0.729±0.045, P<0.05). The 125I seeds induced a higher percentage of apoptosis than that observed in the control in both the SW1990 and PANC-1 cells. The rate of apoptosis increased with increasing radiation dosage. The percentage of apoptosis was slightly higher in the SW1990 cells than in the PANC-1 cells. Dose-dependent G2/M cell-cycle arrest was observed after 125I seed irradiation, with a peak value at 6 Gy. As the dose increased, the percentage of G2/M cell cycle arrest increased in both cell lines, whereas the rate of DNA incorporation decreased. In the 3H-TdR incorporation experiment, the dosimetry results of both the SW1990 and PANC-1 cells decreased as the radiation dose increased, with a minimum at 6 Gy. There were no significant differences in the dosimetry results of the two cell lines when they were exposed to the same dose of radiation. CONCLUSION: The pancreatic cancer cell-killing effects induced by 125I radioactive seeds mainly occurred via apoptosis and G2/M cell cycle arrest.

Genetic variants ofLRRK2 in Taiwanese Parkinson's disease.

Genetic variants of leucine-rich repeat kinase 2 (LRRK2) were reported to alter the risk for Parkinson's disease (PD). However, the genetic spectrum of LRRK2 variants has not been clearly disclosed yet in Taiwanese population. Herein, we sequenced LRRK2 coding region in 70 Taiwanese early onset PD patients (age at onset ≤ 50), and found six amino acid-changing single nucleotide polymorphisms (SNPs, N551K, R1398H, R1628P, S1647T, G2385R and M2397T), one reported (R1441H) and 2 novel missense (R767H and S885N) mutations. We examined the frequency of identified LRRK2 variants by genotyping 573 Taiwanese patients with PD and 503 age-matched control subjects. The results showed that PD patients demonstrated a higher frequency of G2385R A allele (4.6%) than control subjects (2.1%; odds ratio = 2.27, 95% confidence interval: 1.38-3.88, P = 0.0017). Fewer PD patients (27.7%) carried the 1647T-2397T haplotype as compared with the control subjects (33.0%; odds ratio = 0.80, 95% confidence interval: 0.65-0.97, P = 0.0215). However, the frequency of 1647T-2385R-2397T haplotype (4.3%) in PD patients was still higher than in control subjects (1.9%, odds ratio: 2.15, 95% confidence interval: 1.27-3.78, P = 0.0058). While no additional subject was found to carry R767H and R1441H, one more patient was observed to carry the S885N variant. Our results indicate a robust risk association regarding G2385R and a new possible protective haplotype (1647T-2397T). Gene-environmental interaction and a larger cohort study are warranted to validate our findings. Additionally, two new missense mutations (R767H and S885N) regarding LRRK2 in PD patients were identified. Functional studies are needed to elucidate the effects of these LRRK2 variants on protein function.

The validation and application of the Chinese version of perceived nursing work environment scale.

AIMS AND OBJECTIVES: To improve the development of the Chinese version of Perceived Nursing Work Environment (C-PNWE) scale by examination and application and to explore the nurses' perception of their working environment in a hospital. BACKGROUND: The C-PNWE scale was translated and revised from the PNWE scale. The least of perfection is that the development of C-PNWE ignored that the psychometric properties of the PNWE instrument were established of critical care nurses and further application and testing of the PNWE in various patient care settings were recommended. DESIGN: This is a cross-sectional design. Nurses from different departments of a hospital were sampled by convenience sampling and investigated by self-administrated questionnaire. METHODS: Data obtained through questionnaires were analysed by descriptive statistical analyses and profile analyses using the Statistical Package for the Social Sciences (SPSS) Chinese version 17.0 software. RESULTS: The coincident and level profile analyses indicated that these groups can merge into one group, and the profile of measurement result of this merged group would not exhibit flatness. Among six dimensions of C-PNWE scale, the Staffing and Resource Adequacy got the lowest average score. Among 41 items, 'Opportunity for staff nurse to participate in policy decisions' got the lowest mean. CONCLUSIONS: The C-PNWE scale shows good psychometric properties and can be used to explore nurses' perspectives of the nursing practice environment in China. And the situation of nurses' perceived working environment in China needs further study. RELEVANCE TO CLINICAL PRACTICE: Shaping nursing practice environments to promote desired outcomes requires valid and reliable measures to assess practice environments prior to, during and following efforts to implement change. The C-PNWE scale can be a useful measurement tool for administrators to improve the nursing work environment in China.

Anti-proliferative effects of Atractylis lancea (Thunb.) DC. via down-regulation of the c-myc/hTERT/telomerase pathway in Hep-G2 cells.

Atractylis lancea (Thunb.) DC. (AL), an important medicinal herb in Asia, has been shown to have anti-tumor effects on cancer cells, but the involved mechanisms are poorly understood. This study focused on potential effects and molecular mechanisms of AL on the proliferation of the Hep-G2 liver cancer cell line in vitro. Cell viability was assessed by MTT test in Hep-G2 cells incubated with an ethanol extract of AL. Then, the effects of AL on apoptosis and cell cycle progression were determined by flow cytometry. Telomeric repeat amplification protocol (TRAP) assays was performed to investigate telomerase activity. The mRNA and protein expression of human telomerase reverse transcriptase (hTERT) and c-myc were determined by real-time RT-PCR and Western blotting. Our results show that AL effectively inhibits proliferation in Hep-G2 cells in a concentration- and time-dependent manner. When Hep-G2 cells were treated with AL after 48h,the IC50 was about 72.1 µg/ mL. Apoptosis was induced by AL via arresting the cells in the G1 phase. Furthermore, AL effectively reduced telomerase activity through inhibition of mRNA and protein expression of hTERT and c-myc. Hence, these data demonstrate that AL exerts anti-proliferative effects in Hep-G2 cells via down-regulation of the c-myc/hTERT/ telomerase pathway.

ATP13A2 variability in Taiwanese Parkinson's disease.

Mutations in ATP13A2 have been reported to associate with Parkinson's disease (PD). This study investigates the contribution of genetic variants in ATP13A2 to Taiwanese PD. ATP13A2 cDNA fragments from 65 early onset PD (onset <50 years) were sequenced. The identified variants were validated in a cohort of PD (n = 493) and ethnically matched controls (n = 585). A novel heterozygous G1014S, located at the conserved seventh transmembrane domain of ATP13A2 protein, was identified in an early onset PD patient, which was absent in 585 normal controls. Additionally, a reported heterozygous A746T was found in two PD patients and four controls. The clinical features and 99mTc-TRODAT-1 single photon emission computed tomography (SPECT) image of the patients carrying G1014S and A746T were similar to that of idiopathic PD. One normal control with A746T showed an asymmetric reduction of 99mT TRODAT-1 uptake in the right striatum. Under oxidative stress or apoptotic stimulus, lymphoblastoid cells carrying either A764T or G1014S showed increased caspase 3 activity compared with the controls. The rates of decay for G1014S and A746T proteins were more or less reduced in cycloheximide chase experiment. In silico modeling of G1014S exhibited a more stable feature than wild-type, and G1014S is mislocalized mainly in the intralysosomal space, which is coherent with the prediction of prohibiting N-myristoylation and membrane association. We therefore hypothesize that rare variants of ATP13A2 may contribute to PD susceptibility in Taiwan. The role played by ATP13A2 variants in PD remains to be clarified.