Phase 2 Study of Adjuvant Radiotherapy Following Narrow-Margin Hepatectomy in Patients With HCC.

BACKGROUND AND AIMS: Surgical resection is the primary treatment for HCC; however, it is associated with a high rate of recurrence and death. We conducted this phase 2 study to investigate the efficacy and safety of postoperative intensity-modulated radiotherapy (IMRT) for HCC after narrow-margin hepatectomy. APPROACH AND RESULTS: We designed a single-arm, prospective phase 2 trial to evaluate overall survival (OS), disease-free survival (DFS), recurrence patterns, and toxicity in patients receiving adjuvant radiotherapy. The eligibility criteria included the following: pathological diagnosis of HCC after hepatectomy, with narrow pathological margins (< 1 cm); age > 18 years; and Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients received IMRT within 4-6 weeks after surgical resection. This trial was registered at ClinicalTrials.gov (NCT01456156). Between 2008 and 2016, a total of 76 eligible patients who underwent narrow-margin resection were enrolled. The median follow-up duration was 70 months; the 3-year OS and DFS rates were 88.2% and 68.1%, respectively; and the 5-year OS and DFS rates were 72.2% and 51.6%, respectively. Intrahepatic recurrence was the primary recurrence pattern. No marginal recurrence was found. Intrahepatic, extrahepatic, and combined recurrences at the first relapse were found in 33, 5, and 1 patient, respectively. The most common radiation-related grade-3 toxicities were leukopenia (7.9%), elevated alanine aminotransferase (3.9%) and aspartate aminotransferase (2.6%) levels, and thrombocytopenia (1.3%). Classical or nonclassical radiation-induced liver disease was not noted. CONCLUSIONS: Adjuvant radiotherapy is an effective, well-tolerated, and promising adjuvant regimen in patients with HCC who have undergone narrow-margin hepatectomy. Our trial provides evidence and a rationale for planning a future phase 3 trial.

Inhibition of EPS8L3 suppresses liver cancer progression and enhances efficacy of sorafenib treatment.

BACKGROUND: Liver cancer is a devastating disease that has second highest cancer mortality rate worldwide. Although surgical resection or liver transplantation sometimes cures early stage liver cancer, few therapeutic options are available for advanced-stage liver cancer, highlighting the importance of a better understanding of the disease to find novel therapeutic targets. METHODS: Firstly, clinical features of EPS8L3 on liver cancer RNA-seq dataset of The Cancer Genome Atlas (TCGA) database was analyzed, including gene expression levels in tumor tissues in comparison with the normal tissues as well as the patients' OS. To confirm the candidate genes, we used short hairpin RNA (shRNA) to knock down the gene and quantify the cell proliferation, apoptosis, and migration. Then micro-array analysis was did to investigate the intracellular mechanisms of EPS8L3. Moreover, to gain further insights into the translational value of the findings, we treated the liver cancer cells with Sorafenib after knocking down the candidate gene, in order to interrogate the combinatorial inhibitory effects on cell metabolism. RESULTS: As a result, by comparing gene expression profiles of normal liver and cancerous tissues, we find that epidermal growth factor receptor kinase substrate 8-like protein 3 (EPS8L3), a gene with unknown function, is upregulated in liver cancer, and is associated with poor prognosis. Further gene set analyses on liver cancer cells revealed that EPS8L3 is pertinent to cell division and proliferation. Indeed, knocking down EPS8L3 inhibits cell proliferation and migration, and triggers apoptosis in vitro. Additionally, when inoculated into mice, EPS8L3 knocked down cells exhibit slower growth rate. Moreover, EPS8L3 expression can substantially increase the efficacy of low dosage of Sorafenib treatment. Furthermore, the results of immunohistochemical staining of 90 paired liver cancer and adjacent normal samples demonstrated high expression of EPS8L3 yields poor prognosis in Chinese liver cancer patients. CONCLUSIONS: Collectively, our results suggest that EPS8L3 has pivotal oncogenic functions in liver cancer and we propose that EPS8L3 could be a potential therapeutic target to treat liver cancer.

Factors related to self-reported social anxiety symptoms among incoming university students.

AIM: The aim of this study was to explore the lifestyle/social, personality trait and mental factors among incoming university students with higher self-reported social anxiety symptoms (SAS). METHODS: A total of 5126 incoming university students were recruited. The test battery included a self-administered questionnaire that examined personal lifestyle, the Measurement of Support Functions, the Chinese Internet Addiction Scale-Revision, the Organizational Citizenship Behaviour Scale, the Social Phobia Inventory, the suicide ideation from the Brief Symptoms Rating Scale and the Pittsburgh Sleep Questionnaire. RESULTS: SAS (23.7%) were prevalent. Using logistic regression analysis, we found that the significant predictors of higher levels of SAS were being an undergraduate student and a non-smoker, having lower Measurement of Support Functions score (poorer social support), having higher Chinese Internet Addiction Scale-Revision score (Internet addiction), having lower Organizational Citizenship Behaviour Scale score (less altruistic behaviour), having suicide ideation and having higher Pittsburgh Sleep Questionnaire score (poorer sleeper). CONCLUSIONS: Given the high prevalence of SAS among university students, it is necessary to build a better strategy to detect students with potential social anxiety-related problems/disorders or other mental problems early on.

Factors Related to Self-Reported Attention Deficit Among Incoming University Students.

OBJECTIVE: This study was designed to explore physical, social/behavioral, and mental health factors among incoming university students with elevated self-reported ADHD symptoms. METHOD: A total of 5,240 incoming university students were recruited. The test battery included the ADHD Self-Report Scale, the Measurement of Support Functions, the Chinese Internet Addiction Scale-Revision, Quality of Life assessment, the Brief Symptoms Rating Scale, and the 10-item Social Desirability Scale. RESULTS: ADHD symptoms were elevated in 8.6% of the sample. Only individuals with a lower social desirability score, however, were recruited for further analysis. Significant influential factors for higher self-reported levels for ADHD symptoms included greater suicidal ideation and emotional disturbance, as well as a higher Internet addiction tendency, lower levels of social support, and a greater amount of exercise. CONCLUSION: Given the elevated prevalence of self-reported ADHD symptoms among this sample of university students, screening for these kinds of problems to detect early challenges before students fail in college as well as identify youth with undiagnosed ADHD should be considered.

The psychosocial indicators related to neuroticism in both sexes: A study of incoming university students.

Neuroticism may have great impact on mental and physical health in both sexes. The aims of this study were to explore whether relationships between neuroticism scores and psychosocial indicators as well as metabolic syndrome in a population of incoming university students existed in the different sexes. In total, 4266 incoming students were included in this study. The test battery comprised a self-administered structured questionnaire, including the neuroticism subscale of the Maudsley Personality Inventory, the 12-item Chinese Health Questionnaire, the Chinese Internet Addiction Scale-Revision, the measurement of support functions, and the Pittsburgh Sleep Quality Index. Multivariate logistic regression showed that higher Pittsburgh Sleep Quality Index scores, higher Chinese Internet Addiction Scale-Revision scores, and higher 12-item Chinese Health Questionnaire scores were significantly correlated with neuroticism in both sexes, but lower perceived routine support: measurement of support functions scores were associated only with the male participants. No significant differences were found in terms of body mass index or other metabolic profiles. Individuals with poorer mental health and a poorer personal lifestyle had higher neuroticism scores, and sex effects may influence the scale of perceived social support in the neuroticism group. However, the lack of an association between neuroticism score and metabolic syndrome may be due to the recruitment of younger participants in this study.

Perception of premenstrual syndrome and attitude of evaluations of work performance among incoming university female students.

BACKGROUND: Premenstrual syndrome (PMS) is a common condition, and for 5% of women, the influence is so severe as to interfere with their mental health, interpersonal relationships, or studies. Severe PMS may result in decreased occupational productivity. The aim of this study was to investigate the influence of perception of PMS on evaluation of work performance. METHODS: A total of 1971 incoming female university students were recruited in September 2009. A simulated clinical scenario was used, with a test battery including measurement of psychological symptoms and the Chinese Premenstrual Symptom Questionnaire. RESULTS: When evaluating employee performance in the simulated scenario, 1565 (79.4%) students neglected the impact of PMS, while 136 (6.9%) students considered it. Multivariate logistic regression showed that perception of daily function impairment due to PMS and frequency of measuring body weight were significantly associated with consideration of the influence of PMS on evaluation of work performance. CONCLUSION: It is important to increase the awareness of functional impairments related to severe PMS.

Tea-drinking habit among new university students: associated factors.

The habit of drinking tea is highly prevalent in Asian countries. The aim of this study was to investigate the prevalence of tea drinking and to explore the correlated factors on tea drinking among young new students in the university, using a validated self-reported questionnaire. This study was carried out with 5936 new students in a university in Taiwan. It comprised a self-administered structured questionnaire, including items related to personal and medical history, and lifestyle habits, using the Pittsburgh Sleep Quality Index (PSQI) and the 12-item Chinese Health Questionnaire (CHQ-12). Anthropometric measurements and laboratory tests were also performed. In total, 2065 (36.1%) students were in the tea-drinking group. Multiple logistic regression analysis showed the following factors were significant predictors of tea drinking: postgraduate students (p < 0.001), coffee drinking (p < 0.001), alcohol drinking (p < 0.001), minor mental morbidity (p = 0.009), poorer sleepers (p = 0.037), higher body mass index (p = 0.004), and sugar-sweetened beverage consumption (p < 0.001). Our data showed that the tea-drinking habit was correlated with higher body mass index, which was contrary to the findings of a previous study. In clinical practice, perhaps we could consider more tea-drinking-related factors when we suggest tea consumption.

Relative contraindications for percutaneous tracheostomy: from the surgeons' perspective.

PURPOSE: Percutaneous tracheostomy (PT) has gained worldwide acceptance as a bedside procedure by intensivists, but its popularity has declined based on reports of some relative contraindications. The aim of this study was to ascertain the perioperative comorbidities of PT when it is performed by surgeons with experience performing standard tracheostomy. METHODS: Prospective data were collected and analyzed for consecutive PTs performed in intensive care units. RESULTS: No procedure-related mortality occurred in the present study. No significant differences in perioperative comorbidities, such as transient hemodynamic instability and postoperative wound infection, were noted between the relative contraindication (RC) and normal condition (NC) groups. Otherwise, instrument failure (5 cases, p = 0.052) and procedure failure (2 cases, p = 0.222) occurred in the RC group, but not in the NC group. Two patients in the NC group and one patient in the RC group needed to undergo a reoperation to check for bleeding. In a subgroup analysis, more bleeding events were noted for the patients with coagulopathy (p = 0.057), and premature extubation of the endotracheal tube/instrument failure (p = 0.073) was more common in the patients with neck anatomical difficulty in the RC group. CONCLUSIONS: For patients with relative contraindications, the potential of using PT should be determined on an individual basis. Special attention should be paid to the possibility of instrument failure and bleeding events for the patients with relative contraindications for PT.

Social relationship and health among students with low social desirability.

INTRODUCTION: This survey aimed to probe the associations between altruism, social support and subjective health among incoming students with low level of social desirability. METHODS: Totally, 5,634 incoming university students were assessed and 2,472 students with a low tendency toward social desirability were recruited for analysis. RESULTS: The results indicated that altruism and perceived social support were correlated and both could predict subjective health simultaneously. Path analysis indicated that altruism may promote health directly and indirectly by social support. DISCUSSION: Developing curriculums to enhance altruism and social support could be an important issue for university students.

Factors associated with premenstrual syndrome - a survey of new female university students.

Premenstrual syndrome (PMS) can impact an individual's interpersonal relationships, social interactions, productivity, lifestyle, school performance and emotional well-being. This study was designed to explore the factors associated with PMS in new female university students in Taiwan. The test battery included a self-administered structured questionnaire, the five-item brief symptoms rating scale, the Pittsburgh Sleep Quality Index and the Chinese Premenstrual Symptom Questionnaire. Additionally, details of the participants' lifestyles and family and personal histories of physical illness were recorded. Serum lipids were also measured. Of all the participants (N = 1699), 39.85% were defined as having PMS. Using logistical regression analysis, we found a positive relationship between PMS and consuming more foods containing egg yolk, greater alcohol intake, poorer sleep quality, higher likelihood of psychiatric morbidity, family history of dyslipidemia, and a higher serum cholesterol level. The results show that PMS is prevalent among new female university students and that lifestyle and nutritional/metabolic factors may play a role in this disorder.

Engineered autologous bone marrow mesenchymal stem cells: alternative to cleft alveolar bone graft surgery.

Human recombinant bone morphogenetic protein 2 (rhBMP-2) accelerates bone regeneration but is associated with limited cementum and periodontal ligament regeneration, local root resorption, and ankylosis. This study assessed a new approach to the regeneration of the alveolar bone and periodontal attachment apparatus using a combination of ex vivo autologous bone marrow mesenchymal stem cells (MSCs) engineered by replication defective adenovirus to express the BMP-2 gene and pluronic F127 (PF127) in a large mammalian animal model. Bilateral maxillary periodontal defects were created over the premolar area in 9 mature male miniature swine. The 18 defects were randomly assigned to receive either BMP-2-expressing MSCs in the advBMP-2 group or MSCs alone in the MSC group. The regenerated periodontal attachment apparatus was evaluated histologically, and the total regenerated bone volume was calculated from three-dimensional computed tomography analysis. Three months after implantation, significant bone volume was regenerated in the advBMP-2 group. Periodontal apparatus regeneration was significantly better in the advBMP-2 group. New cementum and Sharpey fibers were observed on the denuded root surfaces in the advBMP-2 group, whereas incomplete healing with localized root surface resorption was noted in the control group. The use of ex vivo BMP-2-engineered autologous MSCs enhanced bone and periodontal apparatus regeneration in maxillary alveolar and periodontal defects in swine. This novel integrated approach might be suitable for clinical periodontal apparatus repair. This may be an alternative for cleft alveolar bone graft surgery.

Daily life events influence the results of the Dexamethasone Suppression Test in healthy women.

Although the Dexamethasone Suppression Test (DST) plays an important role in psychosomatic research, confounding factors limit the sensitivity and specificity of the DST. The aim of this study was to investigate the relationship between the intensity of daily life stressors and DST results in healthy participants after controlling the confounding factors. The subjects of this study consisted of 75 healthy volunteers. The intensity of daily life events was assessed using the Taiwanese version of the Recent Life Change Questionnaire (RLCQ). Neuroticism was assessed using the Maudsley Personality Inventory (MPI). The Dexamethasone Suppression Test (DST) was also performed. The regression model showed that daily life events (RLCQ score) were correlated significantly with cortisol level on day 1 and D% only in women. This finding implies that daily life events should be considered as an independent variable in women in further studies when the DST is applied.

A study on the sleep quality of incoming university students.

This study was designed to examine the prevalence and the risk factors of poor sleep quality in 4318 incoming university students in Taiwan. The test battery comprised a self-administered structured questionnaire, including items related to personal medical history and lifestyle habits, the Measurement of Support Functions (MSF), Pittsburgh Sleep Quality Index (PSQI), Chinese Internet Addiction Scale-Revision (CIAS-R), neuroticism subscale of the Maudsley Personality Inventory (MPI), and the 12-item Chinese Health Questionnaire (CHQ-12). Of the total study population, 2360 students (54.7%) were classified into the poor sleep quality group, as defined by a PSQI score ≥6. Based on the results of multivariate logistic regression analysis, poor sleep quality was significantly associated with undergraduate students, female gender, skipping breakfast, tea drinking, a higher tendency toward internet addition, poor social support, higher neuroticism, and higher CHQ scores. Poor sleep quality is prevalent among incoming university students in Taiwan, and more work is needed on the identification of the factors influencing poor sleep, and in providing systematic education in the importance of sleep and time management skills to university students.

Social support and striatal dopaminergic activities: is there a connection?

OBJECTIVES: Although patients' social support is a critical factor for the prognosis of mental disorder treatments, biological mechanisms responsible for the impact of social support remain scarcely explored. We speculated that there may be an association between social support and central dopaminergic activities in humans. METHODS: A total of 65 medicated patients with schizophrenia and their primary first-degree caregivers and 54 healthy volunteers were recruited for Studies 1 and 2, respectively. In Study 1, the extrapyramidal side effects (EPS) of medicated patients with schizophrenia and the social support scores of their caregivers were examined. In Study 2, the availability of striatal D(2)/D(3) receptors, dopamine transporters (DAT) and social support scores were measured in 54 healthy volunteers. RESULT: Study 1: the EPS scores of medicated patients with schizophrenia were negatively correlated with the social support scores of their relatives. Study 2: a positive correlation between the subjective social support scores and striatal DAT availability was noted. CONCLUSION: The central dopaminergic activity may be linked to the sense of social support.

The risk factors of Internet addiction--a survey of university freshmen.

This study was designed to explore the risk factors of Internet addiction in 1360 freshmen of the National Cheng Kung University in Taiwan in 2003. The test battery included a self-administrated structured questionnaire, the Chinese Internet Addiction Scale-Revision (CIAS-R), the 12-item Chinese Health Questionnaire (CHQ-12), the Measurement of Support Functions (MSF), and the neuroticism subscale of the Maudsley Personality Inventory (MPI). Of the total study population, there were 680 college freshmen (17.9%) in the Internet addiction group, as defined by high CIAS-R scores. Using logistic regression analyses, we found positive relationships between Internet addiction and male gender, neuroticism scores and the CHQ score. In addition, the freshmen who skipped breakfast and those who had poorer social support also had a higher probability of Internet addiction. Internet addiction is prevalent among university freshmen in Taiwan. Risk factors included male gender, habit of skipping breakfast, mental health morbidity, deficient social support; and neurotic personality characteristics.

The functionality and economic costs of outpatients with schizophrenia in Taiwan.

The aims of this study were to investigate the economic costs of outpatients with schizophrenia in Taiwan, and to survey factors that influence the costs. The direct costs were defined as the costs associated with psychiatric services and other medical treatment. The indirect costs were estimated using the Human Capital Method. Patients' characteristics, including sex, age, duration of education, duration of illness, frequency of hospitalization, type of antipsychotic medication, severity of extrapyramidal side effects caused by antipsychotic medication, and global functions, were used to estimate the costs. The average annual total cost was approximately US$16,576 per patient. The direct and indirect costs were 13% and 87% of the total costs, respectively. Among the direct costs, folk therapy ranked third, just behind prescription drugs and acute ward hospitalization. The productivity loss of both the patients and their caregivers was the major component of the indirect costs. The patient's age and global functions had a significantly negative relationship with the direct costs. The severity of extrapyramidal side effects, type of antipsychotic medication, and the patient's illness duration correlated positively with the indirect costs, while the patient's global function correlated negatively with the indirect costs. Overall, the indirect costs of treating schizophrenia were higher than the direct costs. Improving patients' functionality and decreasing caregivers' burden are essential to reducing costs.

Influence of meteorological conditions and particulate matter on visual range impairment in Jinan, China.

To understand the influence of aerosol particles and meteorological conditions on visual range in Jinan, the capital of Shandong Province, China, PM(2.5) and PM(10) samples were collected from November 2004 to September 2005. The mass concentrations of PM(2.5) and PM(10), concentrations of water-soluble ions in PM(2.5) and concentrations of black carbon (BC) in the atmosphere were analyzed. The decrease of visual range in Jinan results from the combined influence of PM(2.5), PM(10) and meteorological conditions. For the period studied, the average light extinction coefficient, b(ext), which was estimated from an equation developed by the IMPROVE network was 292 Mm(-1). Ammonium sulfate was the major contributor to visual range impairment, accounting for 41%, while ammonium nitrate, particulate organic matter (POM) and BC made comparable contributions accounting for 20%, 22% and 18%, respectively. This highlights the significance of secondary particles ((NH(4))(2)SO(4), NH(4)NO(3), POM) in visual range impairment in Jinan. The data from this study are also compared with the long-term variations of visual range in Jinan from 1961 to 2005.

Number concentration and size distributions of submicron particles in jinan urban area: characteristics in summer and winter.

The aerosol number concentration and size distribution were measured with the newly developed Wide-range Particle Spectrometer in summer and winter of 2006 at the urban site of Jinan City. Here reported the characteristics of fine particles of the different observation seasons. Relative high number concentrations for the particles in the diameter range of 10-500 nm were observed in both seasons. It was found that the dominant number distributed in particle diameter smaller than 100 nm and the percentage over the number concentration of all air particles is much higher than what has been measured in other urban sites over the world. The number mean diameter in summer was much smaller than in winter, strongly suggesting the different origin of ultrafine particles in different seasons. That is, particles in ultrafine mode mainly came from nucleation and new particle formation in summer while from traffic emission in winter. The diurnal variation also supported this point. Number concentration in the diameter range of 10-200 nm got their peak values at noontime, well correlated with the mixing ratio of SO2 and the intensity of solar radiation in summer. While in winter, those in the same diameter range showed the main peaks during the traffic hours happened in the morning and evening.

Different dimensions of social support for the caregivers of patients with schizophrenia: main effect and stress-buffering models.

The aims of this study were: (i) to assess the impact of caring for patients with schizophrenia on the mental health status of the caregivers; and (ii) to examine the direct and buffer effects of social support on the mental health status of these caregivers. A total of 61 key caregivers of patients with schizophrenia were administered the Chinese Health Questionnaire (CHQ) and the Measure of Support Function (MSF) self-report questionnaire to assess their mental health and social support status. The MSF questionnaire constitutes four subscales, including: (i) the perceived crisis support (PCS); (ii) the perceived routine support (PRS); (iii) the received crisis support (RCS); and (iv) the received routine support (RRS) subscale. The Positive and Negative Syndrome Scale (PANSS) was used to assess the psychopathology severity of the patients they cared for. Then the authors used the hierarchical multiple regression model to analyze the relationship between these variables. The psychopathology severity of the patients reflected by the PANSS scores correlated inversely with the caregivers' CHQ scores. Besides, the PCS subscale scores correlated positively with the caregivers' CHQ scores. Moreover, the interaction between the RCS subscale scores and the PANSS scores was significant. Significant positive correlation between the RCS and CHQ exists only in the higher PANSS subgroup, but not in the lower PANSS subgroup. The psychopathological severity of the patients has a negative impact on their caregivers' mental health. PCS has a direct effect, and RCS has a buffer effect on the mental health status of these caregivers.