A population-based study of the influence of socioeconomic status on prostate cancer diagnosis in Taiwan.

BACKGROUND: Disparities in prostate cancer (PCa) outcomes and their links to socioeconomic status (SES) have been intensively studied. A relatively low incidence rate and a high proportion of late-stage diagnosis have been documented in studies of Asian populations. For the past 20 years, the trend in the growth of PCa cases in Taiwan was opposite to that of Western countries. However, there is a striking paucity of local studies on these important issues. To mitigate this gap in knowledge, we exploited two population databases to investigate the impact of SES on PCa incidence rate and stage at diagnosis. Particularly, we sought to explore the discriminating capabilities of various indexes of SES on two diagnostic outcome indicators. METHOD: We conducted a population-based, follow-up, observational study. Data of study populations and newly diagnosed PCa cases between 2011 and 2013 were collected from the National Health Insurance Research Database and the Taiwan Cancer Registry. We retrieved 50-79 old male subjects who were classified as government employee, enterprise employee, or labor class. People with a diagnosis of any type of cancer before January 1, 2011, were excluded. The influences of four independent variables, i.e., age, beneficiary's insurance status, occupation and income, were analyzed. We used Cox proportional hazard models to calculate the hazard ratios of PCa and used logistic regression models to analyze the odds ratios (ORs) of late-stage PCa diagnosis. RESULTS: The low crude PCa incidence rate (112 per 100,000 person-years) and the high percentage of late-stage presentation (44%) were similar to those found in previous studies of old Asian men. Unsurprisingly, age was consistently revealed to be the most determinant factor in PCa diagnosis, while the insurance status of the beneficiaries showed no significant difference. Significant socioeconomic disparities in PCa diagnosis were demonstrated by occupation and income indexes, individually or in combination. However, occupation and income showed varied capabilities in discriminating disparities between different outcome indicators. CONCLUSION: Our study supported the findings of extant works showing that advantaged populations have a higher PCa incidence rate and a lower percentage of late-stage diagnosis. The discriminating capabilities of health disparity by occupation and/or income were contingent on the choice of health outcome indicators. The relatively high percentage of late-stage presentation is a critical public health challenge, and a tailored coping strategy is urgently needed. For more effective health policy-making, local socioeconomic effects on the other outcome indicators of PCa, such as incidence to mortality ratio, warrant further investigation.

Dual Trajectories of Sleep Duration and Cigarette Smoking during Adolescence: Relation to Subsequent Internalizing Problems.

Decreasing sleep duration and increasing cigarette smoking of adolescents are major public health concerns. However, research examining connections between the developmental trajectories of the outcomes that are evolving contemporaneously and their relation to long-term outcomes is still lacking. This study examined distinct trajectories of sleep duration and cigarette smoking during adolescence, associations between these trajectories, and links with internalizing problems during young adulthood. Data were collected from 2510 adolescents who participated in a longitudinal study spanning from 2006 through 2014 in northern Taiwan. Group-based dual trajectory modeling was used to examine the dynamic relationships between sleep duration and cigarette smoking trajectories during adolescence. Multiple linear regression was used to understand the association between the distinct trajectories and subsequent internalizing problems. Three sleep duration trajectories (short decreasing, typical sleep, and long sleep) and three cigarette smoking trajectories (nonsmokers, late increasing, and escalating smokers) were identified. We found significant inter-relationships for sleep duration and cigarette smoking trajectories during adolescence; all atypical sleep duration trajectories conferred increased risks of increased cigarette smoking and vice versa. In addition, the effects of sleep duration and cigarette smoking on later internalizing problems were found to vary by sex and trajectory patterns. These results provide insight regarding the co-development of sleep duration and cigarette smoking trajectories during adolescence. We also highlight the different roles of sleep duration and cigarette smoking trajectories and their relation to internalizing problems of young adulthood.

Reciprocal relationship between unhealthy eating behaviours and depressive symptoms from childhood to adolescence: 10-year follow-up of the Child and Adolescent Behaviors in Long-Term Evolution study.

OBJECTIVE: To investigate the reciprocal relationship between unhealthy eating behaviours and depressive symptoms from childhood to adolescence. DESIGN: Unhealthy eating behaviours were measured by the frequencies of eating foods with excess salt, sugar or fat in the past week. Depressive symptoms in the past two weeks were measured using a seven-item scale. Hierarchical linear growth models were used to analyse longitudinal associations between unhealthy eating behaviours and depressive symptoms. Time-fixed variables (sex, parents' education level and household monthly income) and time-varying variables (parents' marital status, family activities, body weight, vegetable or fruit consumption, exercising and smoking) were controlled for. SETTING: The Child and Adolescent Behaviors in Long-Term Evolution study, which commenced in 2001 and has annual follow-up. SUBJECTS: Students (n 2630) followed from 2nd grade (8 years old in 2002) to 11th grade. RESULTS: The frequency of unhealthy eating behaviours in the previous year and the difference between the frequency in the previous and successive year were positively associated with the initiation and growth rate of depressive symptoms. Depressive symptoms in the previous year and the difference in depressive symptoms between the previous and successive year were positively associated with the initial state and growth rate of unhealthy eating behaviours. CONCLUSIONS: Our results suggest a reciprocal relationship between depressive symptoms and unhealthy eating behaviours. This relationship should be considered when developing programmes targeting depressive symptoms and unhealthy diet in children and adolescents.

The involvement of nuclear factor-κappaB in the nuclear targeting and cyclin E1 upregulating activities of hepatoma upregulated protein.

Hepatoma upregulated protein (HURP) is originally isolated during the search for the genes associated with hepatoma. HURP is upregulated in many human cancers. Culture cells exhibit transformed and invasive phenotype when ectopic HURP is introduced, revealing HURP as an oncogene candidate. Our previous studies demonstrated that Aurora-A regulated the cell transforming activities of HURP by phosphorylating HURP at four serines. To unravel how the Aurora-A/HURP cascade contributes to cell transformation, we firstly noticed that HURP shuttled between cytoplasm and nucleus. The nuclear localization activity of HURP was promoted or abolished by overexpression or knockdown of Aurora-A. Similarly, the HURP phosphorylation mimicking mutant 4E had higher nuclear targeting activity than the phosphorylation deficient mutant 4A. The HURP 4E accelerated G1 progression and upregulated cyclin E1, and the cyclin E1 upregulating and cell transforming activities of HURP were diminished when the nuclear localization signal (NLS) was removed from HURP. Furthermore, HURP employed p38/nuclear factor-κB (NF-κB) cascade to stimulate cell growth. Interestingly, NF-κB trapped HURP in nucleus by interacting with HURP 4E. At last, the HURP/NF-κB complex activated the cyclin E1 promoter. Collectively, Aurora-A/HURP relays cell transforming signal to NF-κB, and the HURP/NF-κB complex is engaged in the regulation of cyclin E1 expression.

The effects of social structure and social capital on changes in smoking status from 8th to 9th grade: results of the Child and Adolescent Behaviors in Long-term Evolution (CABLE) study.

OBJECTIVE: Social structure and social capital are important variables for public health strategies seeking to prevent smoking among adolescents. The purpose of this study was to examine the relationships between social structure, social capital and changes in smoking status from the 8th to 9th grade in Taiwan. METHODS: Data were obtained from the Child and Adolescent Behaviors in Long-term Evolution (CABLE) project. The study analyzed a final sample of 1937 students (50.7% female). RESULTS: Each layer of social structure was associated with a particular form of social capital. Students whose parents were married and living together had higher family social capital. After controlling for background variables, the social structure variable of friends who smoke was significantly associated with changes in smoking status. Students reporting more school attachment were less likely to start smoking. Students with higher parental supervision was associated with less chance of being a consistent smoker, whereas participation of social organization outside of school was associated with continued smoking. Attending school club was associated with higher probability of smoking cessation. CONCLUSION: Smoking prevention and intervention strategies aimed at junior high school students should be tailored to the particular form of social capital important for each type of smoking status.

The incidence of experimental smoking in school children: an 8-year follow-up of the child and adolescent behaviors in long-term evolution (CABLE) study.

BACKGROUND: Studies have established that most regular adult smokers become addicted in their adolescent years. We investigated the incidence of and risk factors associated with initial experimental smoking among a group of school children who were followed for 8 years. METHODS: We used cohort data collected as part of the Child and Adolescent Behaviors in Long-term Evolution (CABLE) study, which selected nine elementary schools each from an urban area (Taipei City) and a rural area (Hsingchu county) in northern Taiwan. From 2002 to 2008, children were asked annually whether they had smoked in the previous year. An accelerated lifetime model with Weibull distribution was used to examine the factors associated with experimental smoking. RESULTS: In 2001, 2686 4th-graders participated in the study. For each year from 2002 to 2008, their incidences of trial smoking were 3.1%, 4.0%, 2.8%, 6.0%, 5.3%, 5.0% and 6.0%, respectively. There was an increase from 7th to 8th grade (6.0%). Children who were males, lived in rural areas, came from single-parent families, had parents who smoked, and had peers who smoked were more likely to try smoking earlier. The influence of parents and peers on experimental smoking demonstrated gradient effects. CONCLUSIONS: This study used a cohort to examine incidence and multiple influences, including individual factors, familial factors, and community factors, on experimental smoking in adolescents. The findings fit the social ecological model, highlighting the influences of family and friends. School and community attachment were associated with experimental smoking in teenagers.

Tubulozole-induced G2/M cell cycle arrest in human colon cancer cells through formation of microtubule polymerization mediated by ERK1/2 and Chk1 kinase activation.

Our studies demonstrated that human colon cancer cells (COLO 205), with higher expression level of check point kinase 1 (Chk1), were more sensitive to microtubule damage agent Tubulozole (TUBU) induced G2/M phase arrest than normal human colon epithelial (CRL) cells. TUBU (10 microM, for 3h) treatment resulted in rapid and sustained phosphorylation of Cdc25C (Ser-216) leading to increased 14-3-3beta binding. This resulted in increased nuclear translocation. In addition, TUBU induced phosphorylation of the Cdc25C (Ser-216) and Bad (Ser-155) proteins were blocked by Chk1 SiRNA-transfection. Surprisingly, cellular apotosis was observed in cells treated with TUBU after Chk1 SiRNA inhibition. We further demonstrated that extracellular signal-regulated kinase (ERK) activation by TUBU was needed for Chk1 kinase activation and microtubule formation as shown by the attenuation of these responses by the ERK1/2 specific inhibitor PD98059. However, TUBU induced ERK1/2 phosphorylation was not blocked in the Chk1 SiRNA-transfected COLO 205 cells. These results imply that ERK1/2 mediated Chk1 activation may be play an important role in determining TUBU induced G2/M arrest or apoptosis in COLO 205 cells.

Doxapram shortens recovery following sevoflurane anesthesia.

PURPOSE: A randomized, double blind controlled trial was undertaken to investigate the effect of doxapram on recovery times and bispectral index following sevoflurane anesthesia. METHODS: Upon completion of surgery under sevoflurane anesthesia, 60 adult patients were randomly allocated to receive either doxapram hydrochloride 1 mg.kg(-1) iv or saline placebo. Clinical recovery from anesthesia was assessed by time to eye opening on verbal command, hand squeezing on command, time to extubation, and the Aldrete recovery score. Bispectral index values, systolic blood pressure, and heart rate were recorded at baseline (before anesthesia), during surgery, and every minute for 15 min after administration of the study drug. RESULTS: Time to eye opening was shorter in the doxapram group compared with the control group (6.9 +/- 2.2 min vs 9.9 +/- 3.1 min, P < 0.05). Mean bispectral index scores were also higher in the doxapram group compared with the saline placebo seven to eight minutes following administration of the study medication (P < 0.05). More rapid emergence was associated with a greater increase in heart rate with doxapram (P < 0.05 compared with placebo), but no differences in systolic blood pressure responses were observed in comparison with placebo. CONCLUSION: We conclude that doxapram 1 mg.kg(-1) hastens early recovery from sevoflurane anesthesia, and this arousal effect correlates with higher bispectral index values.

Involvement of proapoptotic Bcl-2 family members in terbinafine-induced mitochondrial dysfunction and apoptosis in HL60 cells.

Terbinafine (TB, lamisil), a promising world widely used oral-anti-fungal agent, has been used in the treatment of superficial mycosis. In this study, we found that apoptosis but not cell growth arrest was induced by TB (1 microM, for 24 h) in human promyelocytic leukemia (HL60) cells. The apoptotic effect induced by TB in the HL60 cell was not through the general differentiation mechanisms evidenced by evaluation of three recognized markers, including CD11b, CD33, and morphological features. In addition, our results also revealed that TB-induced apoptosis was not through the cellular surface CD 95 receptor-mediated signaling pathway. We found that the mitochondria membrane in the TB-treated HL60 cells was dissipated by decreasing of the electrochemical gradient (DeltaPsi(m)) led to leakage of cytochrome c from mitochondria into cytosol. Such effects were completely blocked by in vitro transfection of the HL60 cells with Bcl-2 overexpression plasmid (HL60/Bcl-2). However, our data found that TB-mediated apoptosis could not be completely prevented in the Bcl-2 over expressed (HL60/Bcl-2) cells. Such results implied that additional mediators (such as caspase-9) other than mitochondria membrane permeability might contribute to the TB-induced cellular apoptosis signaling. This hypothesis was supported by the evidence that administration of caspases-9 specific inhibitor (z-LEHD-fmk) blocked the TB-induced apoptosis. Our studies highlight the molecular mechanisms of TB-induced apoptosis in human promyelocytic leukemia (HL60) cells.

Characterization of cortical neuron outgrowth in two- and three-dimensional culture systems.

To improve the ability of regeneration by grafting living cells or by adding growth factor to a lesion site, it is important to find good biomaterials for neuron survival and regeneration. This study focused on two- and three-dimensional cultures in a matrix using biomaterials such as agarose, collagen, fibrin, and their mixtures, because these are considered to be suitable biomaterials for neuron outgrowth. Cortical neurons were dissected from E17 rat embryos and cultured in agarose gel, collagen gel, fibrin glue, and mixtures of collagen and fibrin. Results showed that neurons cultured in collagen gel and fibrin glue had longer periods of survival (more than 3 weeks) and better neurite extension than those observed in agarose gels. As to the survival rate according to the MTT and lactate dehydrogenase assays, fibrin glue was the most suitable biomaterial for neuron survival among the biomaterials examined. With two-dimensional fibrin plating, neuron cells exhibited cell aggregation and stress fibers, but the same results were not observed with collagen gel. There were no differences in neurite extension and survival in the mixtures of collagen and fibrin. The results suggest that collagen and fibrin can provide a suitable substrate for a three-dimensional culture matrix for neuronal survival and differentiation.