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Background: The World Health Organization has identified methadone maintenance therapy (MMT) as the most effective treatment for reducing patient dependence on heroin. In Taiwan, MMT has been used as a heroin harm reduction strategy since 2006. Although the effectiveness of MMT in reducing heroin addiction has been examined quantitatively in prison samples, little attention has been paid to the experiences and perspectives of patients with heroin addiction receiving MMT. This study was designed to address this gap in scientific knowledge. Purpose: The aim of this study was to investigate the experiences of individuals struggling with heroin addiction who are receiving MMT in the community. Methods: A qualitative descriptive research approach and semistructured interviews were used in this study. We interviewed 14 participants who had received MMT in a medical center in central Taiwan. All of the interview data were recorded, transcribed, and analyzed using qualitative content analysis. Results: Four themes emerged: (a) a chance to change one's life, (b) the helpfulness of MMT, (c) a sense of being restricted and controlled, and (d) need for support. Conclusions/Implications for Practice: This article fills a gap in current scholarly understanding of patient experiences and their perspectives on the helpfulness of MMT. Understanding patient experiences and perspectives is critical to informing and developing concrete strategies for clinical practice and MMT policy. Clinical professionals should assess patient needs and concerns to determine whether they are met by current treatment programs. Policymakers should design more flexible policies to facilitate easier access by patients to methadone to reduce the risk of relapse. [ABSTRACT FROM AUTHOR]

Although public opinion in Taiwan has shifted to favoring self-determination regarding end-of-life care, many nursing home residents still entrust their end-of-life care decision making to family members. This study examined Chinese cultural impediments to nursing home residents signing advance directives. A descriptive qualitative study was conducted using content analysis. In total, 18 nursing home residents participated in face-to-face interviews. Five main themes were identified: (1) bad omens, (2) inability, (3) traditional culture, (4) uncertainty, and (5) unmet needs. The death taboo that is a prominent feature of Chinese culture and the delivery of generic information are primary impediments. Therefore, health care providers should provide tailored information about advance directives, communicate directly with residents, ensure that residents understand the relationship between signing an advance directive and having a good death, and respect the final decisions of residents. [ABSTRACT FROM AUTHOR]

Background: When older nursing home residents and their families are faced with end-of-life care decisions in Taiwan, they make them in the context of traditional cultural norms and socioeconomic changes. Both parties (residents and their family members) are often unwilling to broach the topic, leading to a decisional impasse. The aim of this study was to understand difficult-to-raise issues related to end-of-life care by investigating the perspectives of older nursing home residents and their family members. Methods: This qualitative descriptive study was conducted using content analysis based on the Consolidated Criteria for Reporting Qualitative Research. Purposive sampling was used to select the participants, and sampling continued until data saturation. Data were collected using semi structured interviews, and related analyses were conducted using an inductive approach. Results: Ten residents and twelve family members were interviewed individually. Six main themes were identified: (1) the inevitability of a goodbye; (2) a good death; (3) going with or against traditional culture; (4) better a good death than a bad life; (5) abiding by the residents' decisions; and (6) being willing but unable to take care of residents. Conclusion: Nursing home residents and their family members' thoughts on end-of-life care shifted toward the concept of a good death, and they even regarded death as a form of liberation. Health care providers may serve as mediators to counsel a resident and their family members separately, enabling them to speak up and understand each other's thoughts on end-of-life care before a decision is made so that neither party has regrets. [ABSTRACT FROM AUTHOR]

Background and Purpose: Intra-islet heparan sulfate (HS) plays an important role in the maintenance of pancreatic islet function. The aim of this study was to investigate the effect mechanism of HS loss on the functioning of islets in diabetic mice.Experimental Approach: The hypoglycaemic effect of a heparanase inhibitor, OGT2115, was tested in a streptozotocin-induced diabetic mouse model. The islets in pancreatic sections were also stained to reveal their morphology. An insulinoma cell line (MIN6) and primary isolated murine islets were used to investigate the effect of OGT2115 in vitro.Key Results: Intra-islet HS was clearly lost in streptozotocin-induced diabetic mice due to the increased heparanase expression in damaged islets. OGT2115 prevented intra-islet HS loss and improved the glucose profile and insulin secretion in streptozotocin-treated mice. The apoptosis of pancreatic beta cells and the infiltration of mononuclear macrophages, CD4- and CD8-positive T-cells in islets was reduced by OGT2115 in streptozotocin-treated mice, but OGT2115 did not alter the direct streptozotocin-induced damage in vitro. The expression of heparanase was increased in high glucose-treated isolated islets but not in response to direct streptozotocin stimulation. Further experiments showed that high glucose stimuli could decreased expression of PPARγ in cultured islets, thereby relieving the PPARγ-induced inhibition of heparanase gene expression.Conclusion and Implications: Hyperglycaemia could cause intra-islet HS loss by elevating the expression of heparanase, thereby aggravating inflammatory cell infiltration and islet damage. Inhibition of heparanase might provide benefit for pancreatic beta cell protection in Type 1 diabetes. [ABSTRACT FROM AUTHOR]

This study aimed to clarify the experiences of family members of older adult residents regarding the signing of an advance directive in the context of a Chinese culture. Twenty family members of older residents in a long-term care facility participated in face-to-face interviews, and the researchers conducted a thematic analysis of observation field notes and interview transcripts. A content analysis of the interviews revealed 4 themes concerning the refusal to sign advance directives: resident decision, group decision, not entitled to decide, and random decision. Health providers may serve as mediators and pass on the residents' views regarding their end-of-life care to their families after holding discussions with residents and their families separately to ensure that an agreeable decision regarding the modes and objectives of EOL care is reached and that such a decision respects the right of the patient to choose. [ABSTRACT FROM AUTHOR]

Background: Psychiatric patients are affected by diseases and mental symptoms that may worsen their ability to adjust emotionally. Being unable to respond to the emptiness, increases the risk of suicidal behaviors. Purpose: This study was designed to translate the Experienced Level of Existential Emptiness (ELEE) scale, developed by Hazell in 1984, from the original English into Chinese and then to test its reliability and validity. Methods: This research adopted a cross-sectional design and collected data using convenience sampling and a structured questionnaire. The subjects of this study were psychiatric outpatients in the acute and chronic wards of a psychiatric hospital in Taiwan. The instruments used in this research included a demographic datasheet; the ELEE; the University of California, Los Angeles Loneliness Scale, version 3; the Beck Depression Inventory-II; the State- Trait Anxiety Inventory Y form; and the Oxford Happiness Inventory. After the data were obtained, the reliability and validity of the Chinese-version scale was tested. Results: Three hundred subjects were surveyed. The content validity index value of the ELEE was between .88 and 1, and the retest reliability and intrinsic consistency were good. From the analysis of criterion-related validity, a higher degree of emptiness was shown to correlate with more-obvious feelings of loneliness, depression, and anxiety. Conversely, a higher sense of happiness was shown to correlate with less-obvious feelings of these three variables. After the construct validity test, which used confirmatory factor analysis and regarded the co-variation coefficient of association and model fit index as the basis of consideration, the scale was reduced to two sub-scales of seven questions each. After the deletion of items, the scale retained good retest reliability and intrinsic consistency, supporting the retention of the 14 questions in the scale. Conclusions/ Implications for Practice: The findings of this study support using the Chinese version of the ELEE to measure emptiness in patients with mental illness and then providing appropriate medical assistance based on the measured results. [ABSTRACT FROM AUTHOR]

Objective: This study sought to develop a decision aid with cartoon pictures and evaluate its effectiveness in increasing consistency between elderly individuals and their surrogates regarding end-of-life care.Methods: A pre-post quasi-experimental design was adopted using the Life Support Preferences Questionnaire. The intervention had two components: (1) increasing participants' knowledge of medical treatments related to end-of-life care, and (2) sharing their end-of-life wishes. The experimental group received an intervention, whereas the control group received usual care.Results: A total of 110 participants in 55 pairs of elderly individuals with average aged 86.4 and their surrogates (27 in the experimental group, 28 in the control group) were recruited from a veterans hospital in northern Taiwan. Nearly 90 % of elderly individuals were male. The multiple linear regression showed that the inconsistent gap between elderly individuals and their surrogates in the experimental group decreased 12 points than the control group after controlling the covariances (B = -12.116, p = 0.032).Conclusion: The intervention improved the consistency between elderly individuals and their surrogates regarding end-of-life care.Practice Implications: A decision aid with cartoon pictures may support the discussion of end-of-life care in older Asian populations. [ABSTRACT FROM AUTHOR]

Background and Aims: The Child-Pugh (CP) score is a widely used method to assess liver function and predict postoperative outcomes in patients with hepatocellular carcinoma (HCC). Recently, the fibrosis index (FIB-4) has been demonstrated to be closely associated with liver fibrosis and cirrhosis. This study aimed to compare the capability of FIB-4 index with CP score in predicting the outcomes for HCC patients after hepatectomy.Methods: A total of 495 HCC patients who underwent hepatectomy were enrolled. The performance of the FIB-4 index in predicting postoperative liver failure (PHLF) and overall survival was compared with that of the CP score.Results: Of them, 9.3% (46/495) patients developed PHLF. The area under the receiver operating characteristic (ROC) curve of the FIB-4 index for predicting PHLF was greater than that of the CP score (0.744 versus 0.621; P = 0.044). The optimal cutoff value of the FIB-4 index for predicting PHLF was 4.16. Multivariable analyses revealed that the FIB-4 index was an independent predictor of PHLF regardless of the hepatectomy subgroups, but the CP grade was only a significant predictor of PHLF in the minor hepatectomy subgroup. The FIB-4 index (4.16) stratified patients into two distinct overall survival cohorts (P = 0.006). The FIB-4 index also classified patients with the Barcelona Clinical Liver Cancer (BCLC) stages 0 and A into two distinct overall survival cohorts (P = 0.001 and P = 0.034, respectively).Conclusion: The FIB-4 index may be a better predictor of PHLF and overall survival in HCC patients with hepatectomy than CP score. [ABSTRACT FROM AUTHOR]

Background: Surrogates often do not accurately predict older people's preferences about end-of-life (EOL) care. Few studies have examined the impact of advance care planning (ACP) on EOL decision-making consistency between older people and their surrogates, and these studies have yielded conflicting results. Objectives: To evaluate the effectiveness of ACP in improving EOL decision-making consistency between older people and their surrogates. Design: The intervention in this pre–post quasi-experimental design included an informative video, a brochure about ACP, and a guided discussion about EOL wishes. Setting: Two geriatric wards in a medical center in northern Taiwan. Subjects: One hundred eight participants, as 54 pairs of older people and their surrogates, were randomly assigned to either the experimental or control group. The experimental group received an intervention, while the control group received usual care. Measurements: Life-Support Preferences Questionnaire. Results: The intervention did not improve decision-making consistency between older people and their surrogates. This was the first time that most pairs discussed specific EOL decisions, so additional preparation may improve comfort with this topic. This study also found that some older people had difficulty concentrating on the educational brochure or understanding the related terms. Conclusions: Preparation for ACP discussion is needed for older people and their surrogates. Longer-term effects of ACP should be monitored because ACP interventions may have enhanced empathy between older people and their surrogates. Additionally, a culturally sensitive illustrated questionnaire that explains life-support preferences and ACP topics may improve communication between older people and their surrogates. [ABSTRACT FROM AUTHOR]

Background: The features and risk analysis of non-alcoholic fatty liver disease (NAFLD) in a community-based setting remain elusive. The predictors between obese and lean subjects need further clarification. We aimed to assess the characteristics of NAFLD during a community screening. The associated metabolic abnormalities and cardiovascular risk assessment were also analyzed.Methods: A total of 2483 subjects receiving multi-purpose health screening at 10 primary care centers were recruited. They received clinical assessment, including demographic data, laboratory examination, and abdominal sonography.Results: The prevalence of NAFLD and metabolic syndrome were 44.5%, and 15.8%, respectively. Among those NAFLD subjects, 1212 (48.8%) subjects were obese (BMI≥ 24 kg/m2). There was an increasing trend of NAFLD according to age, ranging from 25.8% of those aged <30 years to 54.4% of those aged 50-70 years (P for trend< 0.0001). High insulin resistance (IR) was the significant predictive factor for NAFLD in both obese (odds ratio [OR] = 3.85, 95% confidence interval [CI] = 1.87-8.36, P = 0.0002) and lean subjects (OR = 2.52, 95% CI = 1.13-5.54, p = 0.02). The prevalence of high Framingham Risk Score (≥7.5%) was 56.7% (211/372) among the male subjects, which was significantly higher than that (26%, 191/734) of the females (P < 0.001). There was a significant increase of high Framingham Risk Score according to BMI, ranging from 23.1% of BMI<24 kg/m2 to 45% of BMI>27 kg/m2 (P for trend< 0.0001).Conclusion: IR is predictive of NAFLD irrespective of BMI. The cardiovascular risk may exist in lean NAFLD subjects. [ABSTRACT FROM AUTHOR]

Purposes: Clinical trial education has not been extensively integrated into nursing education systems. Acute care nurses may lack sufficient knowledge when caring for admitted trial patients, which may negatively influence their attitudes toward clinical trials. The aim of this study was to explore ward‐based nurses' knowledge and attitudes toward clinical trials. Design and Methods: Ward‐based nurses working in medical, surgical, and intensive care units in a medical center in Taiwan were approached to complete a questionnaire. The questionnaire was developed by the research team and included four parts: demographics, experience with clinical trials, clinical trial knowledge, and attitudes toward clinical trials. Findings: A total of 161 nurses responded. Nearly 90% of the nurses accessed trial information in their workplace. Nearly 80% of the respondents had experience with caring for trial patients, but the mean score of clinical trial knowledge was 4.5 out of a possible score of 10. For attitudes toward clinical trials, the mean score for positive beliefs was 39.7, and the mean score for negative expectations was 42.5, both out of a possible score of 55. The results indicated that respondents typically tended to hold a negative attitude toward clinical trials, especially in regard to the side effects of study drugs and communication with investigators. Conclusions: Knowledge deficits of ward‐based nurses concerning trial participation is apparent. Continuing education for ward‐based nurses is necessary to promote implementation of clinical trials and reduce negative expectations related to clinical trials. Clinical Relevance: One way to improve nurses' knowledge is to integrate clinical trial education into nursing education systems, which will provide more channels through which nurses can understand how a trial works, including the risks, benefits, and participant protection. Through such educational initiatives, ward‐based nurses may develop more positive beliefs regarding clinical trials and provide higher quality clinical trial care to participants. [ABSTRACT FROM AUTHOR]

Objective: This study investigated changes in fat-free mass (FFM) and skeletal muscle 5 years after surgery in participants from the Longitudinal Assessment of Bariatric Surgery-2 trial.Methods: A three-compartment model assessed FFM, and whole-body magnetic resonance imaging (MRI) quantified skeletal muscle mass prior to surgery (T0) and 1 year (T1), 2 years (T2), and 5 years (T5) postoperatively in 93 patients (85% female; 68% Caucasian; age 44.2 ± 11.6 years) who underwent gastric bypass (RYGB), sleeve gastrectomy, or adjustable gastric band. Repeated-measures mixed models were used to analyze the data.Results: Significant weight loss occurred across all surgical groups in females from T0 to T1. FFM loss from T0 to T1 was greater after RYGB (mean ± SE: -6.9 ± 0.6 kg) than adjustable gastric band (-3.5 ± 1.4 kg; P < 0.05). Females with RYGB continued to lose FFM (-3.3 ± 0.7 kg; P < 0.001) from T1 to T5. A subset of males and females with RYGB and MRI-measured skeletal muscle showed similar initial FFM loss while maintaining FFM and skeletal muscle from T1 to T5.Conclusions: Between 1 and 5 years following common bariatric procedures, FFM and skeletal muscle are maintained or decrease minimally. The changes observed in FFM and muscle during the follow-up phase may be consistent with aging. [ABSTRACT FROM AUTHOR]

Rationale: Stratification of asthma at the molecular level, especially using accessible biospecimens, could greatly enable patient selection for targeted therapy.Objectives: To determine the value of blood analysis to identify transcriptional differences between clinically defined asthma and nonasthma groups, identify potential patient subgroups based on gene expression, and explore biological pathways associated with identified differences.Methods: Transcriptomic profiles were generated by microarray analysis of blood from 610 patients with asthma and control participants in the U-BIOPRED (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes) study. Differentially expressed genes (DEGs) were identified by analysis of variance, including covariates for RNA quality, sex, and clinical site, and Ingenuity Pathway Analysis was applied. Patient subgroups based on DEGs were created by hierarchical clustering and topological data analysis.Measurements and Main Results: A total of 1,693 genes were differentially expressed between patients with severe asthma and participants without asthma. The differences from participants without asthma in the nonsmoking severe asthma and mild/moderate asthma subgroups were significantly related (r = 0.76), with a larger effect size in the severe asthma group. The majority of, but not all, differences were explained by differences in circulating immune cell populations. Pathway analysis showed an increase in chemotaxis, migration, and myeloid cell trafficking in patients with severe asthma, decreased B-lymphocyte development and hematopoietic progenitor cells, and lymphoid organ hypoplasia. Cluster analysis of DEGs led to the creation of subgroups among the patients with severe asthma who differed in molecular responses to oral corticosteroids.Conclusions: Blood gene expression differences between clinically defined subgroups of patients with asthma and individuals without asthma, as well as subgroups of patients with severe asthma defined by transcript profiles, show the value of blood analysis in stratifying patients with asthma and identifying molecular pathways for further study. Clinical trial registered with www.clinicaltrials.gov (NCT01982162). [ABSTRACT FROM AUTHOR]

Rationale, aim and objective The beneficial effects of granulocyte colony-stimulating factor (G-CSF) prophylaxis on reducing the risk of chemotherapy-induced febrile neutropenia (CIFN) were well documented throughout the literature. However, existing data regarding its cost-effectiveness were conflicting. We estimated the cost-effectiveness of G-CSF prophylaxis in CIFN under Taiwan's National Health Insurance (NHI) system. Methods Data on clinical outcomes and direct medical costs were derived for 5179 newly diagnosed breast cancer and 629 non-Hodgkin's lymphoma (NHL) patients from the NHI claims database. Patients were further categorized into three subgroups as "primary-", "secondary-" and "no -" prophylaxis based on their patterns of G-CSF use. Generalized estimating equations were applied to estimate the impact of G-CSF use on the incidence of CIFN. The incremental cost-effectiveness ratios of primary and secondary prophylactic G-CSF use were calculated and sensitivity analyses were performed. Results Primary prophylaxis of G-CSF decreased the incidence of CIFN by 27% and 83%, while secondary prophylaxis by 34% and 22% in breast cancer and NHL patients, respectively. Compared with those with no prophylaxis, the incremental cost per CIFN reduced in primary prophylaxis is $931 and $52 among patients with breast cancer and NHL, respectively. In contrast, secondary prophylaxis is dominated by no prophylaxis and primary prophylaxis in both cancer patients. Conclusion Primary but not secondary prophylactic use of G-CSF was cost-effective in CIFN in breast cancer and NHL patients under Taiwan's NHI system. [ABSTRACT FROM AUTHOR]

The article focuses on the aspects of the undergraduate research (UR) program for the professional disciplines at Bridgewater State University. Topics include the various strategies provided by the university to provide pre-professional research opportunities, the UR opportunities offered by the university for several university's courses including education, business management, and social works, and the inclusions of the faculty mentors and students.

Background In the past several decades, Polygonum viviparum L. (PV) was reported to have antibacterial, antiulcer, antioxidant, antitumor, anti-inflammatory, and antiarthritic properties. The antiinflammatory pathway was recently elucidated through cytosolic nuclear factor E2-related factor 2 (Nrf2) activation and heme oxygenase (HO)-1 protein expression. PV is a perennial herb and widely distributed in high-elevation mountain regions, such as the Tibetan Plateau. In Tibetan traditional medicine, PV is usually used to boost the blood circulation to dissipate blood stasis. Therefore, this study focused on how PV improves the vascular circulation and acts on vascular tissues. Methods In this study, we isolated aortas from Sprague-Dawley rats (male, weight about 250 ∼ 350 g), and detected the effects of PV on phenylephrine (PE)-induced contraction and cyclic guanosine 3',5'-monophosphate (cGMP) formation using aortic rings. In addition, human umbilical vein endothelial cells (HUVECs) were used to exam nitric oxygen (NO) synthase (NOS) activity by directly measuring NO production in the culture medium. Endothelial (e) NOS phosphorylation, and cytosolic Nrf2 and HO-1 expressions were measured using a Western blot analysis. Results PV dose-dependently relaxed PE-induced contractions in endothelial-intact but not -denuded aorta. The concentration to produce 50% relaxation was 22.04 ± 1.77 μg/ml. PV-induced vasorelaxation was markedly blocked by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), an NOS inhibitor, methylene blue (MB), a guanylyl cyclase inhibitor, and hemoglobin, an NO scavenger. PV increased cGMP formation; however, this effect was also suppressed by co-pretreatment with L-NAME, MB, hemoglobin, and Ca2+-free medium. In HUVECs, PV increased NO formation, which was greatly attenuated by NOS inhibitors (LNAME and L-NMMA) and by removing extracellular Ca2+ and chelating intracellular Ca2+ with BAPTA-AM. In addition, PV promoted eNOS phosphorylation, Nrf2 degradation, and HO-1 protein expression according to a Western blot analysis. Conclusions The results suggest that PV possesses vasorelaxing action in an endothelium-dependent manner and works through activating Ca2+/calmodulin- dependent NO synthesis; when NO is released and then transferred to smooth muscle cells, NO activates guanylyl cyclase and increases cGMP formation, ultimately resulting in vasorelaxation. Thus, PV can be considered for application as a potential therapeutic approach for vascular-associated disorders. [ABSTRACT FROM AUTHOR]

Background: The hospital-based palliative care team model has been implemented in most Western countries, but this model is new in Taiwan and there is little research to evaluate its outcomes. Objectives: The purpose of this study was to evaluate the effects of the hospital-based palliative care team on the care for cancer patients. Design: The design was a quasi-experimental study with a pretest-posttest design. Setting: A medical center, National Taiwan University Hospital in Taipei, Taiwan. Participants: Cancer patients were excluded after the hospital-based palliative care team visited if they were unable to give informed consent, were not well enough to finish the baseline assessment, were likely to die within 24 h or would be discharged within 24 h, or could not communicate in Mandarin or Taiwanese. A sample of 60 patients who consulted the hospital-based palliative care team was recruited. Methods: Patients recruited to the study were divided to receive the usual care only (control group, n = 30) or the usual care plus visits from the hospital-based palliative care team (intervention group, n = 30). Data were collected using questionnaires including the Symptom Distress Scale, Hospital Anxiety and Depression Scale, Spiritual Well-Being Scale, and Social Support Scale at the initial assessment and one week later. Results: Comparison between groups revealed that the degree change for edema, fatigue, dry mouth, abdominal distention, and spiritual well-being in the intervention group showed significant improvement compared to the control group (p < 0.05). However, there was no difference between groups on measures of anxiety, depression and feeling of social support. Within group analysis showed patients' pain score, dyspnea, and dysphagia improved in both groups (p < 0.05). In addition, the average degree of constipation and insomnia in the control group declined from baseline (p < 0.05), while the degree of edema, fatigue, dry mouth, appetite loss, abdominal distention, and dizziness decreased significantly in the intervention group (p < 0.05). Conclusion: The findings indicated the hospital-based palliative care team can improve the care for patients in relation to symptom management and spiritual well-being. The hospital- based palliative care team is a good care model for patients and worth implementing in clinical practice in Taiwan. The results also provide a general understanding about how the hospital-based palliative care team works in Taiwanese culture. [ABSTRACT FROM AUTHOR]

Aims and objectives To explore the essence of the illness experiences of middle-aged men with oral cancer. Background Having oral cancer creates great challenges in the lives of middle-aged men and their families. Understanding patients' experiences provides a sound basis for patient-centred and individualised care. Research is limited regarding the illness experience of middle-aged men with oral cancer with regard to facing both the invasion of disease and the responsibilities of middle age. Design A phenomenology approach was used. Methods Nine men diagnosed with oral cancer within one year were recruited during 2009 and 2010. Data were collected through individual in-depth interviews and analysed using Colaizzi's phenomenological analysis procedures. Results The following five themes emerged from the patterns of categorised interview data: the psychological journey in facing oral cancer, the question of how patients can control their disease as well as the sequelae of cancer treatment, the continuous disturbance and turmoil resulting from the disease, the appreciation of the support from family and friends, and the ability to learn to actively face the future. Conclusions Patients with oral cancer experienced tremendous physical, psychosocial and financial challenges. Although burdened with multiple stressors, these middle-aged men were able to learn from their experiences and exhibit positive growth in life. Relevance to clinical practice Patients with oral cancer have to constantly adjust to the impact of their disease. The study results may serve as a reference for improving clinical practice and the quality of care among patients with oral cancer. Cancer care is multidimensional and holistic. Healthcare professionals should develop a set of plans by which patients receive complete medical care and support, as well as assistance from professionals and family members, as their treatment progresses to help patients face the challenges of cancer. [ABSTRACT FROM AUTHOR]

Objectives: While the NCCN guidelines maintain that T4b oral cavity squamous cell carcinoma (OCSCC) should undergo either non-surgical treatments or clinical trials, promising outcomes of T4b OCSCC having surgical excision have been reported. We analyzed and compared the clinical outcomes of Taiwanese patients with pT4a and pT4b OCSCC who had undergone surgical treatment.Methods: From 2011 to 2017, a total of 4031 and 355 patients with first primary pT4a and pT4b OCSCC were identified. A propensity score (PS)-matched analysis of patients (n = 351 each) for pT4a and pT4b tumors was also performed.Results: The 5-year disease-specific and overall survival (DSS/OS) rates were more favorable in patients with pT4a than in those with pT4b OCSCC (64%/55%, p < 0.0001; 55%/43%, p < 0.0001, respectively). Compared with pT4a, those with pT4b tumors had a higher burden of the following risk factors: buccal/retromolar/hard palate subsite, male sex, depth ≥ 10 mm, and positive margins. Before PS matching, multivariable analyses revealed that pT4b tumors (versus pT4a) were an adverse prognosticator for both 5-year DSS and OS (hazard ratios: 1.32 and 1.39, respectively). However, in the PS-matched cohort, no significant differences in 5-year DSS and OS rates were observed between pT4a and pT4b OCSCC (57%/56%, p = 0.4024; 48%/44%, p = 0.1807, respectively) CONCLUSIONS: No significant outcome differences were evident between pT4b and pT4a OCSCC after PS matching. The most plausible hypothesis for the observed survival difference between T4a and T4b tumors is that it was driven by positive margins. We suggest that T4b OCSCC should undergo initial surgical excision if adequate resection is possible. [ABSTRACT FROM AUTHOR]

Background: The emotional and spiritual exhaustion experienced by nurses working in intensive care units (ICUs) may decrease quality of care and lead to higher turnover rates among these nurses. However, the lack of a relevant questionnaire to assess the facilitators and barriers perceived by ICU nurses in caring for end-of-life patients hinders further understanding of ICU nurse exhaustion. Purpose: This study developed and tested the psychometric properties of a Chinese-version questionnaire of facilitators and barriers perceived by ICU nurses providing care to end-of-life patients. Methods: This was a three-phase study. The first phase involved translating the English questionnaire into Chinese with original author approval. The second phase used a panel of seven experts to validate questionnaire content. The third and final phase used purposive sampling to recruit 282 ICU nurses to establish the reliability and test-retest reliability of the questionnaire. Results: A content validity index of .95, internal consistency coefficient of .95 and test-retest of .70 were found. Factor analysis showed six barrier factors, which together accounted for 59.2% of total variance and six facilitator factors, which accounted for 63.1% of total variance. Conclusions / Implication for Practice: Results of this study indicate that the Chinese-version questionnaire of facilitators and barriers perceived by ICU nurses in caring for end-of-life patients is a valid and reliable instrument that may be applied in ICU settings to elicit barrier and facilitator factors, which may be used to improve continuing education curricula, enhance quality of care, and reduce ICU nurse turnover. [ABSTRACT FROM AUTHOR]

lo s.-f., hayter m., hu w.-y., tai c.-y., hsu m.-y. & li y.-f. (2012) Symptom burden and quality of life in patients with malignant fungating wounds. Journal of Advanced Nursing 68(6), 1312-1321. Abstract Aim. This study describes the relationship between symptoms and quality of life in patients with malignant fungating wounds. Background. Malignant fungating wounds are complex wounds that can bleed, become malodorous due to infection and are painful causing physical and psychological distress. However, there is a lack of literature on the impact that such wounds can have on quality of life. Methods. This was a descriptive, cross-sectional multi-centre study of patients with malignant fungating wounds. Participants were recruited from the palliative care, hospice, outpatient clinic and oncology units of three medical centres in Taiwan. Data were collected from February 2008 to August 2009. A structured questionnaire obtained socio-demographic information, medical details, wound assessment information and the Taiwanese version of the McGill quality of life questionnaire was administered by interview. Results. McGill quality of life scores indicated that the participants had the lowest quality of life. The participant's age, dressing change frequency, pain, wound dressing comfort, wound symptom, bleeding and malodour had statistically significant negative correlations with quality of life. Multiple regression analysis showed that age, malodour, pain issues and psychological issues explained 87% of the total variance in quality of life. Conclusion. This study contributes to our understanding of the impact of malignant fungating wounds and how correct assessment and management is necessary to improve quality of life. Educational intervention research is needed for patients and caregivers in countries where this has not yet been performed. Further research should also identify whether nursing competence has a direct impact on quality of life. [ABSTRACT FROM AUTHOR]

Background/purpose: Elucidating developmental profiles and temperament patterns in children with cerebral palsy (CP) could help clinicians elaborate more flexible strategies for treating these children. This study investigated the developmental profiles and temperament patterns in children with spastic CP (sCP) of different subtypes and severities.Methods: One hundred and five children, aged 3-6 years, with sCP and 66 children with typical development (TD) were analyzed. Children with sCP were classified into spastic diplegia (SD; n = 60), and spastic quadriplegia (SQ; n = 45) groups. Motor severity was classified via the Gross Motor Function Classification System (GMFCS). Development quotients (DQs) of eight domains and temperament scores of nine dimensions were evaluated.Results: The SQ group had lower DQs in all developmental functions than the SD group (p < 0.01). The DQ distributions of developmental profiles showed the same trend in SD and SQ groups, and both groups displayed lowest DQs in the gross motor domain. The SQ group was less adaptable and approachable than the TD group (p < 0.05), and both sCP groups had lower attention span and persistence and a higher threshold of responsiveness than the TD group (p < 0.05). Correlation analysis showed that GMFCS levels were highly related to all developmental functions (r < -0.54, p<0.01) and weakly related to some temperament dimensions in children with sCP.Conclusion: The subtype and severity of sCP were associated with developmental profiles in children with sCP Temperament patterns were different between SD and SQ groups, but only weakly related to motor deficit. These data could allow clinicians to anticipate the developmental profiles and temperament patterns and plan appropriate therapeutic strategies for children with sCP. [ABSTRACT FROM AUTHOR]

Background and Purpose: Recent evidence has suggested that nicotine decreases blood pressure (BP) and heart rate (HR) in the nucleus tractus solitarii (NTS), indicating that nicotinic acetylcholine receptors (nAChRs) play an important role in BP control in the NTS. However, the signalling mechanisms involved in nAChR-mediated depressor effects in the NTS are unclear. Hence, the aim of this study was to investigate these signalling mechanisms.Experimental Approach: Depressor responses to nicotine microinjected into the NTS of Wistar-Kyoto rats were elicited in the absence and presence of an antagonist of α7 nAChR, the calcium chelator ethylene glycol tetraacetic acid, a calmodulin-specific inhibitor, nitric oxide (NO) synthase (NOS) inhibitor, endothelial NOS (eNOS)-selective inhibitor or neuronal NOS (nNOS)-specific inhibitor.Key Results: Microinjection of nicotine into the NTS produced a dose-dependent decrease in BP and HR, and increased nitrate levels. This depressor effect of nicotine was attenuated after pretreatment with a nAChR antagonist or blockers of the calmodulin-eNOS pathway. In contrast, N5-(1-Imino-3-butenyl)-L-ornithine (vinyl-L-NIO), nNOS-specific inhibitor, did not diminish these nicotine-mediated effects. Calmodulin was found to bind eNOS after nicotine injection into NTS. However, nicotine did not affect the eNOS phosphorylation level or eNOS upstream extracellular signal-regulated kinases (ERK)1/2 and Akt phosphorylation levels. Furthermore, pretreatment with an ERK1/2 or Akt inhibitor did not attenuate nicotine-induced depressor effects in the NTS.Conclusions and Implications: These results suggest that the nAChR-Ca(2+) -calmodulin-eNOS-NO signalling pathway, but not nNOS, plays a significant role in central BP regulation, and neither the ERK1/2 nor Akt signalling pathway are significantly involved in the activation of eNOS by nAChRs in the NTS. [ABSTRACT FROM AUTHOR]

Background/purpose: Data about the clinical manifestations of congenital adrenal hyperplasia caused by 21-hydroxylase deficiency (21-OHD) are lacking in Taiwan. Therefore, this study analyzed the clinical features of 21-OHD in Taiwanese children to improve the diagnosis of this disorder, and to provide background information regarding the ongoing neonatal screening program for 21-OHD in Taiwan.Methods: Eighty children with 21-OHD, 39 with the salt-wasting (SW) type and 41 with the simple-virilizing (SV) type, were evaluated by a review of their medical records. Their clinical symptoms and signs, laboratory findings, and genetic mutations were analyzed.Results: The most frequent features in 21-OHD patients were hyperpigmentation and signs of androgen excess. Clinical manifestations related to hyponatremia such as poor feeding, poor weight gain, and dehydration were noted most frequently in patients with SW-type 21-OHD. Five patients had low serum cortisol with elevated plasma adrenocorticotropic hormone levels, and 22 patients had elevated dehydroepiandrosterone sulfate levels. All had elevated blood levels of 17-hydroxyprogesterone, androstenedione and testosterone. Hyponatremia and hyperkalemia were detected in 29 patients with SW-type 21-OHD. In terms of molecular diagnosis, mutations at IVS2-12A/C --> G and gene deletion were the most frequent mutations detected in SW-type 21-OHD, while I172N and mutation at IVS2-12A/C --> G were most frequent in SV type.Conclusion: Taiwanese children with 21-OHD have characteristic clinical findings such as hyperpigmentation, androgen excess, and failure to thrive. There is a good correlation between genotype and pheno-type. Laboratory tests, including serum 17-hydroxyprogesterone, androstenedione, and testosterone levels are more sensitive than serum cortisol or dehydroepiandrosterone sulfate levels for diagnosing 21-OHD in prepubertal children. [ABSTRACT FROM AUTHOR]

Background/purpose: To understand the importance of autoimmunity in the development of type 1 diabetes in Taiwanese children, we evaluated the presence of beta-cell autoantibodies and their correlation with residual beta-cell function.Methods: From 1989 to 2006, 157 Taiwanese children with newly diagnosed type 1 diabetes were enrolled in this study. We determined the presence of beta-cell autoantibodies, such as glutamic acid decarboxylase autoantibodies (GADAs), insulinoma antigen 2 autoantibodies (IA-2As), and insulin autoantibodies (IAAs). A 6-minute glucagon test was also performed at diagnosis.Results: At diagnosis, 73% of children tested positive for GADAs, 76% for IA-2As and 21% for IAAs. Ninety-two percent of them had at least one of the beta-cell autoantibodies detected. Positivity for IAAs was more frequent in patients younger than 5 years than in those older than 5 years (45% vs. 13%). Using multiple regression analysis, the presence of GADAs or IAAs, or age of onset of these patients was an independent factor for residual beta-cell function. Younger patients and those with GADAs had less residual beta-cell function at disease onset, whereas those with IAAs had more insulin reserve.Conclusion: Autoimmunity plays an important role in the pathogenesis of type 1 diabetes in Taiwanese children, and the presence of IAAs tends to be more common in younger children. [ABSTRACT FROM AUTHOR]

Background/Purpose: Undergraduate medical education lacks standardized curricula for teaching endof-life care and only sporadic curricula evaluations have been reported. The objectives of this study were to evaluate the effect of a multimodal teaching program on preclinical medical students'' knowledge of palliative care, and their beliefs relating to ethical decision-making. Methods: This study had a quasi-experimental design. The teaching formats included didactic lectures, bedside patient care, and interactive discussions. A structured questionnaire evaluated the effects of educational intervention—in terms of knowledge of palliative care and beliefs about common ethical dilemmas relating to end-of-life care in Taiwan. Results: All 118 students who participated in the study completed the questionnaire. Students showed significant improvement (score of 9.97 pre-test vs. 12.73 post-test; p < 0.001) in the 18-item palliative care knowledge questionnaire after educational intervention. Among the four common ethical dilemmas, students'' beliefs of truth-telling (4.22 vs. 4.54; range 1–5; t = −4.66; p < 0.001) and place of care (4.37 vs. 4.52; range 1–5; t =−2.43; p < 0.05) were significantly improved. Logistic regression showed that the improvement in beliefs about ethical decision-making was not significantly influenced by improved knowledge of palliative care. Conclusion: A 1-week multimodal curriculum for preclinical medical students can improve the knowledge and beliefs about ethical decision-making in managing terminally ill patients. Clinical skills of symptom management, especially pain control, and ethical decision-making regarding artificial nutrition and hydration should be emphasized in medical education, to promote students'' competence in end-of-life care. [Copyright &y& Elsevier]

Background/Purpose: Short stature is a common manifestation of Turner syndrome. The purpose of this study was to evaluate the effect of growth hormone (GH) therapy alone on the adult height of children with Turner syndrome. Methods: From 1987 to 2006, 21 Turner syndrome patients who had been treated with GH for > 2 years and had reached adult height were enrolled in the study. The dosage of GH was 0.33 mg/kg/week. Estrogen replacement therapy was prescribed at the age of 15.6 ± 0.9 years, if indicated. The patients had been followed-up until they reached their adult height. During the same period, 28 Turner syndrome patients who were not treated with growth-promoting agents were enrolled for comparison. Mann-Whitney U test and Wilcoxon signed rank test were used for comparison. Results: Twenty-one patients in the study group started GH therapy at the age of 11.5 ± 1.8 years. The duration of GH therapy was 4.0 ± 1.5 years. The growth rate before treatment was 3.8 ± 0.7 cm/year, which increased to 7.1 ± 1.4, 5.4 ± 1.4 and 4.7 ± 0.9 cm/year during the first 3 years of GH therapy, respectively. Patients who received GH reached an adult height of 150.0 ± 5.1 cm, which was significantly higher than the 144.7 ± 5.9 cm of the control group (p < 0.05). The adult height of the study group was 6.3 ± 3.3 cm taller than their projected adult height upon enrolment. No major adverse events were detected during GH therapy. Conclusion: GH alone is safe and effective for the promotion of growth in children with Turner syndrome in Taiwan. [Copyright &y& Elsevier]

This study evaluates the effects of glucagon 30 mug/kg (maximal 1 mg) on beta-cell function in children by C-peptide determined before and 6 min after intravenous administration. From 1990 to 2005, 118 Taiwanese children with newly diagnosed diabetes mellitus (98 children with type 1 and 20 children with type 2) and 29 normal Taiwanese children were enrolled in this study. Fasting and 6-min post-glucagon C-peptide levels were analyzed. In the pre-pubertal group, the median fasting serum C-peptide levels were 0.2 and 0.8 nmol/l in type 1 diabetes and normal children, respectively. These levels rose to 0.3 and 1.9 nmol/l after glucagon stimulation. In the pubertal group, the median fasting serum C-peptide levels were 0.3, 1.0 and 0.9 nmol/l in type 1 diabetes, type 2 diabetes and normal children, respectively. They rose to 0.4, 2.5 and 2.7 nmol/l after glucagon stimulation. Both fasting and post-glucagon C-peptide levels in type 1 diabetes patients were significantly lower than those of normal children and children with type 2 diabetes. The optimal cut-off values to distinguish type 1 diabetes patients from those with type 2 as determined by the receiving operating characteristic curve were 0.7 and 1.1 nmol/l, respectively. The sensitivities of both C-peptide values were 93%. The post-glucagon C-peptide level was more powerful in distinguishing type 1 diabetes from type 2 diabetes with higher specificity (95% vs. 85%). The 6-min glucagon test is valuable in assessing beta-cell function in children and can help pediatricians in the differential diagnoses of diabetes mellitus in children. [ABSTRACT FROM AUTHOR]

Goals Of Work: To identify the willingness, influencing factors, and educational needs of community physicians in providing palliative care in the rural areas of Taiwan.Methods: A questionnaire was sent to all medical directors of the 140 government health stations assigned to the rural areas of Taiwan.Results: The overall response rate was 62.8% with 85 valid questionnaires retrieved. The majority of respondents (84.7%) expressed a willingness to provide palliative care if they encountered an advanced cancer patient. However, they would limit their services to consultation and referral (93.0% and 87.5%, respectively), and were less likely to provide home visits (40.3%) or bereavement support of the family (29.2%). With respect to knowledge, the accurate answers to the philosophy/principles and clinical practice of palliative care were 93.4% and 57.3%, respectively. Regarding attitudes, the highest score item in perceiving the threat about providing palliative care was "uncomfortable to meet and take care of the advanced cancer patient." The highest score item in perceiving barriers was "providing palliative care may shorten patient's life, just like euthanasia." The results of stepwise logistic regression analysis for the willingness to provide home visits showed that only the subjective norms remained in the model (OR = 1.87, 95% CI = 1.17-3.01). Educational needs expressed by the respondents were ranked as follows: emotional support to, communication skills with, and bereavement support for the advanced cancer patients and their relatives.Conclusions: Effective training courses that emphasize the practical knowledge of palliative care for community physicians, incorporating palliative care into medical education particularly in terms of communication skills and ethical roles, and active health policy administration including insurance payments, are important for the enhancement of community palliative care in Taiwan. [ABSTRACT FROM AUTHOR]

Pathologic diagnosis of nasopharyngeal carcinoma (NPC) can be challenging since most cases are nonkeratinizing carcinoma with little differentiation and many admixed lymphocytes. Our aim was to evaluate the possibility to identify NPC in nasopharyngeal biopsies using deep learning. A total of 726 nasopharyngeal biopsies were included. Among them, 100 cases were randomly selected as the testing set, 20 cases as the validation set, and all other 606 cases as the training set. All three datasets had equal numbers of NPC cases and benign cases. Manual annotation was performed. Cropped square image patches of 256 × 256 pixels were used for patch-level training, validation, and testing. The final patch-level algorithm effectively identified NPC patches, with an area under the receiver operator characteristic curve (AUC) of 0.9900. Using gradient-weighted class activation mapping, we demonstrated that the identification of NPC patches was based on morphologic features of tumor cells. At the second stage, whole-slide images were sequentially cropped into patches, inferred with the patch-level algorithm, and reconstructed into images with a smaller size for training, validation, and testing. Finally, the AUC was 0.9848 for slide-level identification of NPC. Our result shows for the first time that deep learning algorithms can identify NPC. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between restless legs syndrome (RLS) and hypertension in men and women based on a community-based cohort of middle-aged and elderly participants.Methods: This cross-sectional observational study enrolled 4080 participants from the Sleep Heart Health study (SHHS). RLS was defined by positive responses on a self-administered questionnaire assessing the four diagnostic criteria, with symptoms occurring at least five times per month and associated with at least moderate distress. Hypertension was defined as SBP ≥140 mmHg, DBP ≥90 mmHg, or current use of antihypertensive medication. Propensity score-matched (PSM) inverse probability treatment weighting (IPTW) analyses and multivariable logistic regression were used to examine the relationship between RLS and hypertension.Results: RLS was present in 6.8% of women (n = 152) and 3.2% of men (n = 59). In the primary cohort analysis, the odds ratio (OR) for hypertension was 1.60 [95% confidence interval (CI) 1.19-2.16, p < 0.001] for participants with RLS compared to those without RLS. In the PSM analyses, the OR for hypertension was 1.66 (95% CI 1.09-2.54, p = 0.019) for participants with RLS compared to those without RLS. In sex subgroup analyses, the association between RLS and hypertension persisted in women. In the PSM cohort, the ORs for hypertension were 1.67 (95% CI 1.01-2.81, p = 0.048) and 1.85 (95% CI 0.75-4.75, p = 0.191) in women and men, respectively. Similar results were found in IPTW cohort.Conclusions: This study revealed a positive association between RLS and hypertension in a community-based population; in sex subgroup analyses, the association persisted in women. [ABSTRACT FROM AUTHOR]

Background: Serum anti-phospholipase A2 receptor (PLA2R) antibody was correlated with disease activity of membranous nephropathy(MN). The predictive value of antibody titer changes on immunosuppressive response remains unknown. We investigated predictive value of dynamic change of anti-PLA2R antibody and 24-h urine protein (24hUP) for clinical response of MN.Methods: This was a retrospective cohort study including 47 Chinese MN patients with positive anti-PLA2R antibody in a tertiary referral hospital between January 2012 and March 2014. Patients received cyclophosphamide (CTX, n = 23), or cyclosporine (CYA, n = 24) regimen, respectively. We monitored serum anti-PLA2R titer and 24hUP at one, three and six-month follow-up.Results: At baseline, total patients were 42 ± 14 years old with 29/18 male/female ratio. The median 24hUP was 5.80(3.56,9.41) g/d. The median baseline anti-PLA2R antibody titer was 66.4(31.9, 188.0) RU/mL. Baseline 24hUP and eGFR between subgroups were not significantly different. The differences of relative reduction between antibody titer and 24hUP at one month were statistically significant (CTX group 94.2% vs. 46.8%, P < 0.001; CYA group 54.6% vs. 4.6%, P = 0.04). Only in CTX group, the relative reduction of 24hUP at one month was correlated with composite remission at six-month(P = 0.03). Area under the curve of 24hUP relative reduction in CTX group at one-month for predicting composite remission at six months was 0.85(95%CI 0.65~1.05, P = 0.04). The cutoff value of one-month's 24hUP relative reduction for predicting six-month's composite remission in CTX group was 15.3%, with high sensitivity (83.3%) and specificity (100%).Conclusions: Compared with relative reduction of antibody titer, relative reduction of 24hUP at one-month follow-up in CTX group had a better predictive value for six-month's composite remission. [ABSTRACT FROM AUTHOR]

Alteration of visual scanpaths under emotional facial expression in schizophrenia patients has been described in recent years; however, it is not clear whether such results are different when they transfer to faces in natural social scenes. The present study was designed to investigate the effects of emotional faces in natural social scenes on the gaze patterns of patients with schizophrenia, compared to gaze at isolated faces. A novel theme identification task was used where participants selected a positive, neutral or negative word to describe an emotional picture. Participants were 29 patients with schizophrenia and 31 healthy controls. The Positive and Negative Syndrome Scale (PANSS) and the Scale of Social Function in Psychosis Inpatients (SSPI) were used to assess symptoms and social functioning. In total, patients with schizophrenia showed significantly fewer fixations, saccades numbers and decreased fixations in areas of interest. As expected, patients showed shorter scanpath length, but only in the pictures with social settings. Furthermore, the effect size of scanpaths parameters under social scene was all greater than isolated face. In addition, patients compared to controls showed more abnormal scanpath parameters processing negative and neutral faces than positive faces, especially in social scene. The present study suggests that scanpath length for social scene faces may be more sensitive than for isolated face pictures. Our findings further support restricted scanpath whilst recognizing emotional facial expressions in natural social scenes as a favorable topic for further investigation as a trait marker. [ABSTRACT FROM AUTHOR]

Background: Nursing professionals have received comprehensive medical education and training. However, whether these medical professionals exhibit positive patient care attitudes and behaviors and thus reduce mortality risks when they themselves are diagnosed with chronic diseases is worth exploring. This study compared the mortality risks of female nurses and general patients with diabetes and elucidated factors that caused this difference.Methods: A total of 510,058 female patients newly diagnosed with diabetes between 1998 and 2006 as recorded in the National Health Insurance Research Database were the participants in this study. Nurses with diabetes and general population with diabetes were matched with propensity score method in a 1:10 ratio. The participants were tracked from the date of diagnosis to 2009. The Cox proportional hazards model was utilized to compare the mortality risks in the two groups.Results: Nurses were newly diagnosed with diabetes at a younger age compared with the general public (42.01 ± 12.03 y vs. 59.29 ± 13.11 y). Nevertheless, the matching results showed that nurses had lower mortality risks (HR: 0.53, 95 % CI: 0.38-0.74) and nurses with diabetes in the < 35 and 35-44 age groups exhibited significantly lower mortality risks compared with general patients (HR: 0.23 and 0.36). A further analysis indicated that the factors that influenced the mortality risks of nurses with diabetes included age, catastrophic illnesses, and the severity of diabetes complications.Conclusion: Nurses with diabetes exhibited lower mortality risks possibly because they had received comprehensive medical education and training, may had more knowledge regarding chronic disease control and change their lifestyles. The results can serve as a reference for developing heath education, and for preventing occupational hazards in nurses. [ABSTRACT FROM AUTHOR]

Androgen receptor (AR) targeting is an important therapeutic strategy for treating prostate cancer. Most tumors progress to castration-resistant prostate cancer (CRPC) and develop the neuroendocrine (NE) phenotype under androgen deprivation therapy (ADT). The molecular basis for NE transdifferentiation after ADT remains incompletely understood. Herein, we show that an immunocyte expression protein, ZBTB46, induces inflammatory response gene expression and contributes to NE differentiation of prostate cancer cells. We demonstrated a molecular mechanism whereby ZBTB46 can be regulated by the androgen-responsive gene, SPDEF, and is associated with NE prostate cancer (NEPC) differentiation. In addition, ZBTB46 acts as a transcriptional coactivator that binds to the promoter of prostaglandin-endoperoxide synthase 1 (PTGS1) and transcriptionally regulated PTGS1 levels. Overexpression of ZBTB46 decreases the sensitivity of the combination of enzalutamide and a PTGS1 inhibitor; however, knockdown of ZBTB46 sensitizes the PTGS1 inhibitor and reduces tumor malignancy. ZBTB46 is inversely correlated with SPDEF and is increased in higher tumor grades and small-cell NE prostate cancer (SCNC) patients, which are positively associated with PTGS1. Our findings suggest that the induction of ZBTB46 results in increased PTGS1 expression, which is associated with NEPC progression and linked to the dysregulation of the AR-SPDEF pathway. [ABSTRACT FROM AUTHOR]

Background: Remodeling of the extracellular matrix (ECM) is a hallmark of heart failure (HF). Our previous analysis of the secretome of murine cardiac fibroblasts returned ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5) as one of the most abundant proteases. ADAMTS5 cleaves chondroitin sulfate proteoglycans such as versican. The contribution of ADAMTS5 and its substrate versican to HF is unknown.Methods: Versican remodeling was assessed in mice lacking the catalytic domain of ADAMTS5 (Adamts5ΔCat). Proteomics was applied to study ECM remodeling in left ventricular samples from patients with HF, with a particular focus on the effects of common medications used for the treatment of HF.Results: Versican and versikine, an ADAMTS-specific versican cleavage product, accumulated in patients with ischemic HF. Versikine was also elevated in a porcine model of cardiac ischemia/reperfusion injury and in murine hearts after angiotensin II infusion. In Adamts5ΔCat mice, angiotensin II infusion resulted in an aggravated versican build-up and hyaluronic acid disarrangement, accompanied by reduced levels of integrin β1, filamin A, and connexin 43. Echocardiographic assessment of Adamts5ΔCat mice revealed a reduced ejection fraction and an impaired global longitudinal strain on angiotensin II infusion. Cardiac hypertrophy and collagen deposition were similar to littermate controls. In a proteomics analysis of a larger cohort of cardiac explants from patients with ischemic HF (n=65), the use of β-blockers was associated with a reduction in ECM deposition, with versican being among the most pronounced changes. Subsequent experiments in cardiac fibroblasts confirmed that β1-adrenergic receptor stimulation increased versican expression. Despite similar clinical characteristics, patients with HF treated with β-blockers had a distinct cardiac ECM profile.Conclusions: Our results in animal models and patients suggest that ADAMTS proteases are critical for versican degradation in the heart and that versican accumulation is associated with impaired cardiac function. A comprehensive characterization of the cardiac ECM in patients with ischemic HF revealed that β-blockers may have a previously unrecognized beneficial effect on cardiac chondroitin sulfate proteoglycan content. [ABSTRACT FROM AUTHOR]

Purpose: The evidence for adjuvant therapy of oral cavity squamous cell carcinoma (OCSCC) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. Here, we examined whether adjuvant therapy should be guided by a detailed analysis of pathologic risk factors in patients with pure OCSCC.Methods and Materials: Between 2004 and 2016, we retrospectively reviewed 1200 consecutive patients with OCSCC who underwent radical surgery and neck dissection in the Chang-Gung Memorial Hospital (CGMH). Patients were divided into 3 prognostic groups. High-risk patients were those with extranodal extension (ENE) and/or positive margins (ENE/margins+, n = 267). Intermediate-risk patients were further divided into 3 subgroups: (1) patients in whom adjuvant therapy was indicated according to the CGMH but not the NCCN guidelines (NCCN[-]/CGMH[+], n = 14); (2) patients in whom adjuvant therapy was indicated by the NCCN but not the CGMH guidelines (NCCN[+]/CGMH[-], n = 160); and (3) patients in whom adjuvant therapy was indicated according to both guidelines (NCCN[+]/CGMH[+], n = 411). Low-risk patients were those for whom adjuvant therapy was not suggested in light of either guideline (NCCN[-]/CGMH[-], n = 348).Results: According to NCCN guidelines, postoperative adjuvant therapy was indicated in 69.8% of the participants. However, only 57.7% of patients were in need of adjuvant therapy by CGMH guidelines. The following 5-year outcomes were observed in the NCCN(-)/CGMH(-), NCCN(-)/CGMH(+), NCCN(+)/CGMH(-), NCCN(+)/CGMH(+), and ENE/margins+ subgroups: locoregional control, 88%/70%/83%/79%/68%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P = .576); distant metastases, 2%/7%/2%/9%/36%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P = .003); disease-specific survival, 97%/86%/94%/84%/56%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P < .001); and overall survival, 92%/86%/87%/68%/42%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P < .001), respectively.Conclusions: Patients in the NCCN(+)/CGMH(-) subgroup, 28% (160/571[160 + 411]) of NCCN intermediate-risk patients, had more favorable 5-year disease-specific and overall survival (94% and 87%) than the NCCN(+)/CGMH(+) subgroup. The former are unlikely to derive clinical benefits from NCCN guidelines. The 70% adjuvant therapy rate required by NCCN guidelines after radical surgery might be too high, ultimately leaving room for improvement. [ABSTRACT FROM AUTHOR]

Background: Extranodal natural killer T-cell lymphoma (NKTCL; nasal type) is an aggressive malignancy with a particularly high prevalence in Asian and Latin American populations. Epstein-Barr virus infection has a role in the pathogenesis of NKTCL, and HLA-DPB1 variants are risk factors for the disease. We aimed to identify additional novel genetic variants affecting risk of NKTCL.Methods: We did a genome-wide association study of NKTCL in multiple populations from east Asia. We recruited a discovery cohort of 700 cases with NKTCL and 7752 controls without NKTCL of Han Chinese ancestry from 19 centres in southern, central, and northern regions of China, and four independent replication samples including 717 cases and 12 650 controls. Three of these independent samples (451 cases and 5301 controls) were from eight centres in the same regions of southern, central, and northern China, and the fourth (266 cases and 7349 controls) was from 11 centres in Hong Kong, Taiwan, Singapore, and South Korea. All cases had primary NKTCL that was confirmed histopathologically, and matching with controls was based on geographical region and self-reported ancestry. Logistic regression analysis was done independently by geographical regions, followed by fixed-effect meta-analyses, to identify susceptibility loci. Bioinformatic approaches, including expression quantitative trait loci, binding motif and transcriptome analyses, and biological experiments were done to fine-map and explore the functional relevance of genome-wide association loci to the development of NKTCL.Findings: Genetic data were gathered between Jan 1, 2008, and Jan 23, 2019. Meta-analysis of all samples (a total of 1417 cases and 20 402 controls) identified two novel loci significantly associated with NKTCL: IL18RAP on 2q12.1 (rs13015714; p=2·83 × 10-16; odds ratio 1·39 [95% CI 1·28-1·50]) and HLA-DRB1 on 6p21.3 (rs9271588; 9·35 × 10-26 1·53 [1·41-1·65]). Fine-mapping and experimental analyses showed that rs1420106 at the promoter of IL18RAP was highly correlated with rs13015714, and the rs1420106-A risk variant had an upregulatory effect on IL18RAP expression. Cell growth assays in two NKTCL cell lines (YT and SNK-6 cells) showed that knockdown of IL18RAP inhibited cell proliferation by cell cycle arrest in NKTCL cells. Haplotype association analysis showed that haplotype 47F-67I was associated with reduced risk of NKTCL, whereas 47Y-67L was associated with increased risk of NKTCL. These two positions are component parts of the peptide-binding pocket 7 (P7) of the HLA-DR heterodimer, suggesting that these alterations might account for the association at HLA-DRB1, independent of the previously reported HLA-DPB1 variants.Interpretation: Our findings provide new insights into the development of NKTCL by showing the importance of inflammation and immune regulation through the IL18-IL18RAP axis and antigen presentation involving HLA-DRB1, which might help to identify potential therapeutic targets. Taken in combination with additional genetic and other risk factors, our results could potentially be used to stratify people at high risk of NKTCL for targeted prevention.Funding: Guangdong Innovative and Entrepreneurial Research Team Program, National Natural Science Foundation of China, National Program for Support of Top-Notch Young Professionals, Chang Jiang Scholars Program, Singapore Ministry of Health's National Medical Research Council, Tanoto Foundation, National Research Foundation Singapore, Chang Gung Memorial Hospital, Recruitment Program for Young Professionals of China, First Affiliated Hospital and Army Medical University, US National Institutes of Health, and US National Cancer Institute. [ABSTRACT FROM AUTHOR]

Background: Hypoglycemia is recognized as a limiting factor in diabetes management. Fear of experiencing hypoglycemia may lead to lower quality of life, impaired glycemic control, and emotional distress, all of which impair the ability of patients to self-manage their diabetes effectively. Problem solving is central to diabetes self-management and may help patients achieve effective self-care of their disease. Purpose: The aim of this study was to investigate the ability of people with diabetes to avoid hypoglycemia and to explore associated factors. Methods: A cross-sectional, descriptive designwas used for the study. Data were collected using a demographic and disease characteristics datasheet, the Hypoglycemic Problem Solving Scale, and the Disease-Associated Negative Mood Scale. Results: Three hundred thirteen participants were recruited, with amean age of 55.49 years. The average itemscore for the questions on hypoglycemic problem-solving ability was 2.43 (SD = 0.75). In comparing Hypoglycemic Problem Solving Scale subscales, participants scored highest on the problem orientation subscales and lowest on the problem-solving skills subscales. Multiple regression analysis revealed that being younger and unmarried and having a higher level of education, a diagnosis of Type 1 diabetes, and a lower negative mood score were each significantly associated with greater problem-solving ability as regards hypoglycemic events. Conclusions/Implications for Practice: We suggest that patients with diabetes, especially those who are older or with lower levels of education, receive disease-related psychological interventions and that healthcare professionals teach problemsolving abilities in conjunction with hypoglycemia management. [ABSTRACT FROM AUTHOR]

Aim of the study: Chinese herbal medicine has been used for the treatments of various diseases for years. However, it is often difficult to analyze their biological activities and molecule mechanisms because of their complex nature. In this study, we applied DNA microarray to analyze the biological events induced by herbal formulae, predict the therapeutic potentials of formulae, and evaluate the safety of formulae. Materials and methods: Mice were administrated orally with 15 formulae for 7 consecutive days, and the gene expression profiles in liver or kidney were further analyzed by transcriptomic tools. Results: Our data showed that most formulae altered the metabolic pathways, such as glutathione metabolism and oxidative phosphorylation, and regulatory pathways, such as antigen processing and presentation and insulin-like growth factor signaling pathway. By comparing the gene expression signatures of formulae with those of disease states or drugs, we found that mice responsive to formula treatments might be related to disease states, especially metabolic and cardiovascular diseases, and drugs, which exhibit anti-cancer, anti-inflammatory, and anti-oxidative effects. Moreover, most formulae altered the expression levels of cytochrome p450, glutathione S-transferase, and UDP glycosyltransferase genes, suggesting that caution should be paid to possible drug interaction of these formulae. Furthermore, the similarities of gene expression profiles between formulae and toxic chemicals were low in kidney, suggesting that these formulae might not induce nephrotoxicities in mice. Conclusions: This report applied transcriptomic tools as a novel platform of translational medicine for Chinese herbal medicine. This platform will not only for understanding the therapeutic mechanisms involving herbal formulae and gene interactions, but also for the new theories in drug discovery. [Copyright &y& Elsevier]

Background: The prevalence and incidence of end-stage renal disease (ESRD) in Taiwan are the highest of any country in the world. The different renal replacement therapies that are adopted by patients with ESRD significantly affect their social roles and daily life. However, because of the complexities of different renal replacement therapies, patients may be unsure of which to choose. Purpose: The aim of this study was to explore the effectiveness of a shared decision-making (SDM) program regarding different renal replacement therapies for patients with chronic kidney disease. Methods: A quasi-experimental design was conducted at two similar regional hospitals in Miaoli County, Taiwan. One hospital hosted the intervention group, and the other hospital hosted the control group. The 31 participants in the intervention group took part in a SDM program. The 36 control group participants took part in the pre-ESRD care program. Data collection included demographic and disease characteristics, decisional conflict scale, and decision self-efficacy scale. Results were analyzed using independent t test, Fisher's exact test, generalized estimating equation, and paired t tests. Results: The study results revealed that the intervention group experienced a significant increase in decision self-efficacy and a significant decrease in decisional conflict at 1 month after receiving the SDM intervention in comparison to before and immediately after receiving the intervention. Moreover, the intervention group had higher decision self-efficacy and lower decisional conflict than the control group. Conclusions/Implications for Practice: The SDM program may be an effective intervention for complex decision-making processes, such as the process involved in making renal replacement treatment decisions. The SDM program group intervention improved decisional conflict and decision self-efficacy. Thus, to improve patients' decision-making processes, the application of an SDM program focused on the personal values and opinions of patients with ESRD will be necessary. Physicians and case managers of patients with ESRD should act in complementary and cooperative roles in SDM programs. [ABSTRACT FROM AUTHOR]