Combined oral 5-azacytidine and romidepsin are highly effective in patients with PTCL: a multicenter phase 2 study.

Peripheral T-cell lymphomas (PTCLs) are uniquely vulnerable to epigenetic modifiers. We demonstrated in vitro synergism between histone deacetylase inhibitors and DNA methyltransferase inhibitors in preclinical models of T-cell lymphoma. In a phase 1 trial, we found oral 5-azacytidine and romidepsin to be safe and effective, with lineage-selective activity among patients with relapsed/refractory (R/R) PTCL. Patients who were treatment naïve or who had R/R PTCL received azacytidine 300 mg once per day on days 1 to 14, and romidepsin 14 mg/m2 on days 8, 15, and 22 every 35 days. The primary objective was overall response rate (ORR). Targeted next-generation sequencing was performed on tumor samples to correlate mutational profiles and response. Among 25 enrolled patients, the ORR and complete response rates were 61% and 48%, respectively. However, patients with T-follicular helper cell (tTFH) phenotype exhibited higher ORR (80%) and complete remission rate (67%). The most frequent grade 3 to 4 adverse events were thrombocytopenia (48%), neutropenia (40%), lymphopenia (32%), and anemia (16%). At a median follow-up of 13.5 months, the median progression-free survival, duration of response, and overall survival were 8.0 months, 20.3 months, and not reached, respectively. The median progression-free survival and overall survival were 8.0 months and 20.6 months, respectively, in patients with R/R disease. Patients with tTFH enjoyed a particularly long median survival (median not reached). Responders harbored a higher average number of mutations in genes involved in DNA methylation and histone deacetylation. Combined azacytidine and romidepsin are highly active in PTCL patients and could serve as a platform for novel regimens in this disease. This trial was registered at www.clinicaltrials.gov as #NCT01998035.

Recognition memory impairments and amyloid-beta deposition of the retrosplenial cortex at the early stage of 5XFAD mice.

Early diagnosis and treatment of AD are critical for delaying its progression. The present study, therefore, examined the cognitive status and neuropathological characteristics of 4-month-old 5X familial AD (5XFAD) transgenic (Tg) mice, as an early stage of AD animal model. The novel object recognition task was performed with retention tests at varying intervals (i.e., 10 min, 1 h, 4 h, and 24 h) to measure the retention capacity of recognition memory of 5XFAD mice. At the 4h retention interval, 5XFAD mice exhibited worse performances than non-Tg control mice. Therefore, using amyloid-beta (Aß) 42- and 4G8-immunoreactive plaques, the accumulation of Aß was examined in the gray and white matter of the system that was necessary for the retention of recognition memory, with a focus on the hippocampus and retrosplenial cortex. The expression of ionized calcium-binding adapter molecule-1 (Iba-1) was also examined to measure microglial activation. The immunohistological analysis of Aß and Iba-1 revealed that the retrosplenial cortex was the most affected region in the brains of 4-month-old 5XFAD mice. These findings indicate that the cognitive and neuropathological characteristics of 4-month-old 5XFAD mice would provide a research platform for studying early diagnosis and treatment of AD.

Relationship between Shift Work and Subclinical Hypothyroidism

Background@#To date, only a few studies have reported the relationship between shift work and subclinical hypothyroidism. Therefore, this study aimed to investigate this relationship. Subclinical hypothyroidism is defined as normal thyroxine (free T4) and thyrotropin (thyroid stimulating hormone, TSH) levels above 10 mU/L. @*Methods@#This study included 12,126 male participants who visited Ulsan University Hospital health promotion center from March 1, 2016 to February 28, 2017. Participants answered a self-administered survey about their marital status, educational level, smoking habits, alcohol intake, and frequency of physical activity. Venous blood sampling was performed after maintaining fasting state for at least 8 hours to test for fasting glucose, hemoglobin A1c, total cholesterol, TSH, and free T4. @*Results@#The TSH level was significantly higher in shift workers than that in the non-shift workers, whereas free T4 level did not show any difference between the two groups. In the shift work group, the odds ratio for subclinical hypothyroidism was significantly higher (odds ratio, 1.99, 95%; confidence interval, 1.16–3.40). This result persisted after adjusting for covariates of age, body mass index, educational level, smoking habits, alcohol intake, and frequency of physical activity. @*Conclusion@#The odds of subclinical hypothyroidism were higher in the shift work group. Therefore, clinicians should pay more attention to detect subclinical hypothyroidism in shift workers.

Oral 5-azacytidine and romidepsin exhibit marked activity in patients with PTCL: a multicenter phase 1 study.

The peripheral T-cell lymphomas (PTCLs) are uniquely sensitive to epigenetic modifiers. Based on the synergism between histone deacetylase inhibitors and hypomethylating agents that we established in preclinical PTCL models, we conducted a phase 1 study of oral 5-azacytidine (AZA) and romidepsin (ROMI) in patients with advanced lymphoid malignancies, with emphasis on PTCL. According to a 3 + 3 design, patients were assigned to 1 of 7 cohorts with AZA doses ranging from 100 mg daily on days 1 to 14 to 300 mg daily on days 1 to 21, ROMI doses ranging from 10 mg/m2 on days 8 and 15 to 14 mg/m2 on days 8, 15, and 22, with cycles of 21 to 35 days. Coprimary end points included maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). We treated a total of 31 patients. The MTD was AZA 300 mg on days 1 to 14 and ROMI 14 mg/m2 on days 8, 15, and 22 on a 35-day cycle. DLTs included grade 4 thrombocytopenia, prolonged grade 3 thrombocytopenia, grade 4 neutropenia, and pleural effusion. There were no treatment-related deaths. The combination was substantially more active in patients with PTCL than in those with non-T-cell lymphoma. The overall response rate in all, non-T-cell, and T-cell lymphoma patients was 32%, 10%, and 73%, respectively, and the complete response rates were 23%, 5%, and 55%, respectively. We did not find an association between response and level of demethylation or tumor mutational profile. This study establishes that combined epigenetic modifiers are potently active in PTCL patients. This trial was registered at www.clinicaltrials.gov as NCT01998035.

Relationship between Obesity and Serum 25-Hydroxyvitamin D Concentrations

BACKGROUND: Vitamin D has been known to play an important role in calcium homeostasis and bone metabolism. It has also been implicated in diabetes mellitus, cardiovascular disease, and immune diseases. Several cross-sectional studies conducted worldwide have found that vitamin D is negatively correlated with obesity. In Korea, however, the results of similar studies were found to be inconsistent.METHODS: The study consisted of 585 adults over 18 years of age, who visited a health promotion center at a university hospital from March, 2015 to February, 2016 and their serum vitamin D levels were recorded. They were divided into two groups according to their sex. The correlation coefficients were calculated using Pearson correlation analysis between obesity and vitamin D. Finally, subjects with vitamin D levels less than <20 ng/mL were classified as deficient. Bivariate logistic regression analysis was used to determine the odds ratio of vitamin D deficiency.RESULTS: We observed a significant negative correlation between obesity and vitamin D (P<0.05) among the women but not in the men. The following are the details of the findings: ≥25 in body mass index (model 3 adjusted odds ratio [OR], 4.11; 95% confidence interval [CI], 1.59–10.67), ≥85 cm in waist circumference (model 3 adjusted OR, 1.81; 95% CI, 1.02–4.01), ≥30% in body fat (model 3 adjusted OR, 2.29; 95% CI, 1.17–4.62).CONCLUSION: Based on the results of this study, we suggest that obesity and vitamin D are negatively correlated and that obesity in women predisposes them to vitamin D deficiency.

Association between Benign Prostate Hyperplasia and Occupational Group

BACKGROUND: Insufficient physical activity is well known to increase benign prostate hyperplasia (BPH). However, only few studies have been conducted on the relationship between occupational physical activity and BPH. This study aimed to investigate the relationship between occupational physical activities and BPH in South Korea.METHODS: The study subjects included 4,102 workers who visited the health promotion center at Ulsan University Hospital and underwent transrectal ultrasonography between January 2016 and December 2017. The subjects were divided into two groups according to occupational physical activity (manual or non-manual workers). BPH was defined as a prostate volume of >25 mL. We performed a multivariate regression analysis to investigate the associations between the occupational groups and BPH. In addition, we divided the subgroups according to age and body mass index and analyzed the relationship between occupational physical activities and BPH in each subgroup.RESULTS: The risk of BPH was significantly higher in the non-manual workers than in the manual workers. This result was consistent after adjusting for other risk factors of BPH (odds ratio, 1.26; 95% confidence interval, 1.05–1.51). Likewise, in the subgroup analysis according to age and body mass index, the non-manual workers had higher BPH risk than the manual workers.CONCLUSION: The risk of BPH was significantly higher in the non-manual workers than in the manual workers. To prevent BPH, more attention should be paid to the physical activities and education of non-manual workers.

A phase 1 study of romidepsin and pralatrexate reveals marked activity in relapsed and refractory T-cell lymphoma.

Peripheral T-cell lymphomas (PTCL) are a group of rare malignancies characterized by chemotherapy resistance and poor prognosis. Romidepsin and pralatrexate were approved by the US Food and Drug Administration for patients with relapsed/refractory PTCL, exhibiting response rates of 25% and 29% respectively. Based on synergy in preclinical models of PTCL, we initiated a phase 1 study of pralatrexate plus romidepsin in patients with relapsed/refractory lymphoma. This was a single institution dose-escalation study of pralatrexate plus romidepsin designed to determine the dose-limiting toxicities (DLTs), maximum tolerated dose, pharmacokinetic profile, and response rates. Patients were treated with pralatrexate (10 to 25 mg/m2) and romidepsin (12 to 14 mg/m2) on 1 of 3 schedules: every week × 3 every 28 days, every week × 2 every 21 days, and every other week every 28 days. Treatment continued until progression, withdrawal of consent, or medical necessity. Twenty-nine patients were enrolled and evaluable for toxicity. Coadministration of pralatrexate and romidepsin was safe, well tolerated, with 3 DLTs across all schedules (grade 3 oral mucositis × 2; grade 4 sepsis × 1). The recommended phase 2 dose was defined as pralatrexate 25 mg/m2 and romidepsin 12 mg/m2 every other week. Twenty-three patients were evaluable for response. The overall response rate was 57% (13/23) across all patients and 71% (10/14) in PTCL. The phase 1 study of pralatrexate plus romidepsin resulted in a high response rate in patients with previously treated PTCL. A phase 2 study in PTCL will determine the efficacy of the combination. This trial was registered at www.clinicaltrials.gov as #NCT01947140.

Plasma REST: a novel candidate biomarker of Alzheimer's disease is modified by psychological intervention in an at-risk population.

The repressor element 1-silencing transcription (REST) factor is a key regulator of the aging brain's stress response. It is reduced in conditions of stress and Alzheimer's disease (AD), which suggests that increasing REST may be neuroprotective. REST can be measured peripherally in blood plasma. Our study aimed to (1) examine plasma REST levels in relation to clinical and biological markers of neurodegeneration and (2) alter plasma REST levels through a stress-reduction intervention-mindfulness training. In study 1, REST levels were compared across the following four well-characterized groups: healthy elderly (n=65), mild cognitive impairment who remained stable (stable MCI, n=36), MCI who later converted to dementia (converter MCI, n=29) and AD (n=65) from the AddNeuroMed cohort. REST levels declined with increasing severity of risk and impairment (healthy elderly>stable MCI>converter MCI>AD, F=6.35, P<0.001). REST levels were also positively associated with magnetic resonance imaging-based hippocampal and entorhinal atrophy and other putative blood-based biomarkers of AD (Ps<0.05). In study 2, REST was measured in 81 older adults with psychiatric risk factors for AD before and after a mindfulness-based stress reduction intervention or an education-based placebo intervention. Mindfulness-based training caused an increase in REST compared with the placebo intervention (F=8.57, P=0.006), and increased REST was associated with a reduction in psychiatric symptoms associated with stress and AD risk (Ps<0.02). Our data confirm plasma REST associations with clinical severity and neurodegeneration, and originally, that REST is modifiable by a psychological intervention with clinical benefit.

Effects of ethics education on moral sensitivity of nursing students.

BACKGROUND: While nursing ethics education is commonly provided for undergraduate nursing students in most nursing colleges, consensus on the content and teaching modules for these ethics courses have still not been established. OBJECTIVES: This study aimed to examine the effects of nursing ethics education on the moral sensitivity and critical thinking disposition of nursing students in Korea. RESEARCH DESIGN: A one-group pre- and post-test design was used. Moral sensitivity was measured using the Korean version of the Moral Sensitivity Questionnaire. Critical thinking disposition was measured using the Critical Thinking Disposition Questionnaire. Participants and research context: Participants were 70 undergraduate nursing students who were attending a university located in Seoul, Korea. The nursing ethics education was provided 7 times, from September to December 2010, and comprised 90-min sessions each week. Ethical considerations: This study was conducted in accordance with the Human Subject Research Ethics Committee guidelines. FINDINGS: After the education, the levels for the patient-oriented care, a sub-domain of moral sensitivity, and inquisitiveness, a sub-domain of critical thinking disposition, significantly improved. There were no changes in overall scores for moral sensitivity and critical thinking disposition. There were significant positive correlations between moral sensitivity and critical thinking disposition both pre- and post-intervention. CONCLUSION: These results reflect the need for ongoing efforts to develop innovative content, structure, and instructional methods for undergraduate nursing ethics education programs.

Blood metabolite markers of neocortical amyloid-ß burden: discovery and enrichment using candidate proteins.

We believe this is the first study to investigate associations between blood metabolites and neocortical amyloid burden (NAB) in the search for a blood-based biomarker for Alzheimer's disease (AD). Further, we present the first multi-modal analysis of blood markers in this field. We used blood plasma samples from 91 subjects enrolled in the University of California, San Francisco Alzheimer's Disease Research Centre. Non-targeted metabolomic analysis was used to look for associations with NAB using both single and multiple metabolic feature models. Five metabolic features identified subjects with high NAB, with 72% accuracy. We were able to putatively identify four metabolites from this panel and improve the model further by adding fibrinogen gamma chain protein measures (accuracy=79%). One of the five metabolic features was studied in the Alzheimer's Disease Neuroimaging Initiative cohort, but results were inconclusive. If replicated in larger, independent studies, these metabolic features and proteins could form the basis of a blood test with potential for enrichment of amyloid pathology in anti-amyloid trials.

Factors affecting mobility in community-dwelling older Koreans with chronic illnesses.

PURPOSE: This descriptive study aims to describe the levels of mobility in community-dwelling older Koreans with chronic illnesses, and to examine the associations of their mobility with sleep patterns, physical activity and physical symptoms including fatigue and pain. METHODS: The participants were a total of 384 community-dwelling older adults recruited from three senior centers in Seoul, Korea. Measures included mobility assessed using 6-minute walk test (6MWT), physical activity behavior, sleep profiles, fatigue and pain. Data were collected from July to December 2012. RESULTS: The mean 6MWT distance was 212.68 meters. Over 90% of the study participants (n = 373) were classified as having impaired mobility using 400 meters as the cutoff point diagnostic criteria of normal mobility in 6MWT. The 6MWT distance was 246.68 meters for participants in their 60s, 212.32 meters for those in their 70s, and 175.54 meters for those in their 80s. Significant predictors of mobility included younger age, taking mediation, regular physical activity, female gender, higher income, higher fatigue and better perception on sleep duration, which explained 18% of the total variance of mobility. CONCLUSIONS: A high-risk group for mobility limitation includes low income, sedentary older men who are at risk for increased fatigue and sleep deficit. Further research should incorporate other psychological and lifestyle factors such as depression, smoking, drinking behavior, and/or obesity into the prediction model of mobility to generate specific intervention strategies for mobility enhancement recommendations for older adults.

Predictors of patient satisfaction with tertiary hospitals in Korea.

This study examined the general and system-related predictors of outpatient satisfaction with tertiary health care institutions in Korea. A cross-sectional descriptive study design was employed. The subjects were 1,194 outpatients recruited from 29 outpatient clinics of a university medical center in Korea. Measurements included 5 outpatient service domains (i.e., doctor service, nurse service, technician service, convenience, and physical environment of facility) and patient satisfaction. Of the five domains, nurse service was the domain with the highest mean score (M = 4.21) and convenience was the domain with the lowest mean score (M = 3.77). The most significant predictor of patient satisfaction was the constructs of convenience (ß = 0.21). The results of this study suggest that the concept of patient satisfaction with health care institutions in modern hospitals reflects an integrative process that includes not only the concerned health care personnel but also improved convenience such as user-friendly reservation system and comfortable waiting areas.

Corrigendum to "Factors Affecting Mobility in Community-dwelling Older Koreans with Chronic Illnesses" Asian Nurs Res 9 (2015) 7-13

The authors regret that in the above article it requires a change in the Acknowledgment section.

Factors Affecting Mobility in Community-dwelling Older Koreans with Chronic Illnesses

PURPOSE: This descriptive study aims to describe the levels of mobility in community-dwelling older Koreans with chronic illnesses, and to examine the associations of their mobility with sleep patterns, physical activity and physical symptoms including fatigue and pain. METHODS: The participants were a total of 384 community-dwelling older adults recruited from three senior centers in Seoul, Korea. Measures included mobility assessed using 6-minute walk test (6MWT), physical activity behavior, sleep profiles, fatigue and pain. Data were collected from July to December 2012. RESULTS: The mean 6MWT distance was 212.68 meters. Over 90% of the study participants (n = 373) were classified as having impaired mobility using 400 meters as the cutoff point diagnostic criteria of normal mobility in 6MWT. The 6MWT distance was 246.68 meters for participants in their 60s, 212.32 meters for those in their 70s, and 175.54 meters for those in their 80s. Significant predictors of mobility included younger age, taking mediation, regular physical activity, female gender, higher income, higher fatigue and better perception on sleep duration, which explained 18% of the total variance of mobility. CONCLUSION: A high-risk group for mobility limitation includes low income, sedentary older men who are at risk for increased fatigue and sleep deficit. Further research should incorporate other psychological and lifestyle factors such as depression, smoking, drinking behavior, and/or obesity into the prediction model of mobility to generate specific intervention strategies for mobility enhancement recommendations for older adults.

Mobility of older palliative care patients with advanced cancer: a Korean study.

PURPOSE: to describe the levels of mobility in older cancer patients receiving palliative care in Korea, and to examine the associations of their mobility with lifestyle factors (sleep disturbance, physical activity) and physical symptoms (pain, fatigue). METHODS: In this cross-sectional descriptive study, 91 older cancer patients receiving palliative care were interviewed using a semi-structured survey questionnaire. Mobility was measured using the 6MWT. Physical activity behavior was measured using the classification of the ACSM. Sleep disturbance was assessed using the frequency sub-category of the SHQ. Both pain and fatigue were measured using a VAS. RESULTS: The mean 6MWT distance was 220.38 m. Participants in their 60 s, 70 s, and 80 s walked, on average, 260.93 m, 205.31 m, and 157.05 m, respectively. Approximately 73% of the participants engaged in regular physical activity. Those engaged in regular physical activity were significantly more mobile than those who were not (t = 2.44; p = .017). Higher levels of mobility were correlated with lower levels of sleep disturbance (r = -.37), fatigue (r = -.23), and pain (r = -.27). Significant predictors for mobility included levels of sleep disturbance, medication status, age, number of family members and monthly income, accounting for 34.7% of the variance in mobility. CONCLUSIONS: Korean cancer patients have relatively low levels of mobility. Cancer patients aged over 80 years are a vulnerable group at risk for impaired mobility. Older palliative care patients are more active than one might expect. Levels of mobility are inversely associated with pain, fatigue, and sleep-related symptoms.

A Motivational Physical Activity Intervention for Improving Mobility in Older Korean Americans.

There has been limited empirical support for interventions designed to promote physical activity targeting mobility in racially diverse older adults. This study aims to examine the effects of a Motivational Physical Activity Intervention (MPAI) on social resource, behavioral change process, physical activity, and mobility variables in sedentary older Korean Americans. A quasi-experimental, repeated-measure, pre- and post-tests design was used. Sixty-four community-dwelling, sedentary older Korean Americans (n = 33 for MPAI group, n = 31 for Attention Control group) participated in the study. There were significant improvements in social resources, including social support from family and friends; behavioral change process variables, including self-efficacy; motivational appraisal; and self-regulation for physical activity. There were significant intervention effects on physical activity, walking endurance, and flexibility. The MPAI is supported as improving mobility and physical activity, as well as increasing motivation for physical activity in older Korean Americans.

Moral sensitivity and critical thinking disposition of nursing students in Korea.

This study aimed to examine the level of moral sensitivity and critical thinking disposition among baccalaureate nursing students in Korea. A convenience sample of 142 undergraduate nursing students was surveyed on moral sensitivity using the Korean version of the Moral Sensitivity Questionnaire (K-MSQ) and on critical thinking disposition using the Critical Thinking Disposition Questionnaire (CTDQ). Data were collected from June 2009 to July 2010. Mean score was 2.83 out of 7 on the K-MSQ (relatively low) and 3.70 out of 5 on the CTDQ (relatively high), indicating the need for nursing educators to continue to develop and incorporate strategies that enhance moral sensitivity into ethics courses in undergraduate nursing programs in Korea. Nursing students who regarded nursing as a lifelong career exhibited stronger critical thinking disposition than did students who considered nursing to be a temporary or premarital job. Moral sensitivity should be further emphasized in nursing ethics courses in undergraduate nursing programs in Korea.

Association between physical activity and metabolic syndrome in older adults in Korea: analysis of data from the Korean National Health and Nutrition Examination Survey IV.

The prevalence of metabolic syndrome is consistently increasing among Korean adults and is reported to be particularly high among older adults in Korea. This paper reports the prevalence of metabolic syndrome and identifies the association between metabolic syndrome and physical activity in Korean older adults. Subjects of this study were 3653 older adults who participated in the fourth Korean National Health and Nutrition Examination Survey during the years 2007-2009. The prevalence of metabolic syndrome in the study population was 46.84%. The prevalences of abdominal obesity, elevated fasting glucose, elevated triglycerides, reduced high-density lipoprotein cholesterol, and elevated blood pressure were 39.51, 45.53, 39.55, 48.24, and 69.14%, respectively, in the study population. Compared to subjects who reported low levels of physical activity, the odds ratios of metabolic syndrome for those who were moderately active and highly active were 0.93 and 0.63, respectively. Nurses should develop metabolic syndrome management programs that are tailored to the needs of the targeted group and that include individually adapted physical activity programs to promote health.

The Development and Evaluation of a New Educational Program, Introduction to Clinical Nursing, for Third Year Nursing Students / 기본간호학회지

PURPOSE: The purpose of this study was to evaluate the effects of a newly developed Introduction to Clinical Nursing (ICN) program on critical thinking skills, communication competence, self-efficacy, and clinical performance self-confidence in nursing students in their third year. METHODS: One group pre-test and post-test design was used with three data collection time points (pre-test, post-test1 and post-test2). Participants were 74 third year nursing students approaching their first clinical practicum. The new program included (a) simulated clinical encounters regarding situations of assessing hospitalized patents and caring for patients with oxygenation needs, (b) objective structured clinical examination of skills, (c) lectures, and (e) field trips. Data were analyzed using paired t-tests. RESULTS: After the ICN course, critical thinking skills(significant only between pretest and post-test2), communication competence, and clinical performance self-confidence improved significantly (p<.05). There was no improvement in the self-efficacy total score but there was significant improvement in the subscale, self-regulatory efficacy. CONCLUSIONS: The study results indicate that the ICN course may be effective in increasing critical thinking skills, communication competence, and clinical performance self-confidence in nursing students. However, the effect size was very small and modifications of this program should be considered to develop more cost-effective educational programs.

Validity and reliability of the index of self-regulation scale for physical activity in older korean americans.

The Korean version of the index of self-regulation (KISR) is a nine-item scale designed to measure individuals' level of self-regulation for physical activity. The purpose of this study was to test the psychometric properties of the KISR, including reliability and validity, in a group of older Korean Americans. The KISR was administered to a sample of older Korean Americans at a baseline interview (Time 1) and 12 week followup (Time 2). The internal consistency of the KISR was high at both time points, with Cronbach's alphas of .94 and .95, respectively. The test-retest reliability was moderate-to-high at .68. There was evidence of construct validity of the KISR based on its moderate to high significant correlations with theoretically relevant variables, including motivational appraisal and self-efficacy for physical activity. A principal axis factoring with an oblique rotation resulted in two factors, explaining 89% of the variance. The KISR is a reliable and valid measure to assess the level of self-regulation for physical activity behavior in older Korean Americans.