Relationship Between Athletes' History of Stressors and Sport Injury: A Systematic Review and Meta-Analysis.

A history of stressors in athletes represents psychosocial factors that may lead to sport injury. However, empirical studies have provided varying results for the relationship between stress history and sport injury. We examined prior literature on the stress history - sport injury relationship within a systematic review and, by meta-analysis, we offered a pooled estimate of the strength of this relationship. We searched seven major academic databases (Sportdiscus, Psyinfo, Academic Search Premier, Ovid, Scopus, Web of Science, and PubMed) from January 2000 to September 2023 and identified 19 empirical studies that examined injuries in sports contexts for meta-analysis. In 19 empirical studies of moderate to high publication quality, we found moderate heterogeneity (Q(17) = 98.61; p < .001), low sensitivity (I2 77.82-83.77), and low publication bias (Z-value = 7.74; p < .001). Further, using a random effect estimate-r, we found a low but significant correlation between stress history and sport injury, yielding a small overall effect size (ES) of r = .12. Furthermore, moderation analyses found adolescents (r = .14), contact-sport athletes (r = .09), non-elite athletes (r = .13), and non-European athletes (America r = .16; Asia r = .14; Oceania r = .14) to have a relatively higher ES than their counterparts in this stress history/sport injury relationship. We concluded that inevitable life stressors may lead to many negative consequences for athletes, such that sports professionals should provide stress management educational programs to enhance athletes' health and well-being.

Toxicological evaluation of the red mold rice extract, ANKASCIN 568-R: 13-week chronic toxicity, and genotoxicity studies.

ANKASCIN 568-R is an extract derived from red mold rice (RMR) fermented using Monascus purpureus NTU 568. RMR fermented using M. purpureus NTU 568 prevents cardiovascular diseases and decreases blood lipid levels. This study evaluates the safety of ANKASCIN 568-R, since it has not determined yet. After daily oral ANKASCIN 568-R for 13 consecutive weeks, we evaluated the toxicity tolerance of Sprague-Dawley rats and performed dose formulation analysis on monascin and ankaflavin. The dose formulation analysis showed that ANKASCIN 568-R concentrations were lower than the target concentration and out of range ( ± 15%) at week 8 and on the last dosing day for both monascin (all dose groups) and ankaflavin at the 100 mg/kg dose. The lowest reported concentrations for the low, middle, and high dose formulations were 34.7, 115.2, and 398.1 mg/mL, respectively. We also evaluated the genotoxicity of ANKASCIN 568-R and showed no genotoxicity potential at all ANKASCIN 568-R doses investigated. The no observed adverse effect level of ANKASCIN 568-R was determined to be 796.2 mg/kg/day. This study revealed the first toxicity evaluation data of ANKASICN 568-R, and the data demonstrated ANKASICN 568-R was safe and can be used in daily life.

Motivation, Segmented Physical Activity, Sedentary Behavior, and Weight Status in Adolescents: A Path Analysis.

Purpose: The purpose of this study was to examine the relationships linking motivational variables with BMI percentile (BMI%) via segmented physical activity (PA) and sedentary behavior (SB) in adolescents using path analysis. Method: Secondary data analysis was performed using participants from the Family, Life, Activity, Sun, Health, and Eating (FLASHE) study. A non-probability panel balanced to the US population on sex, Census division, household income and size, and race/ethnicity were screened for eligibility. The final sample consisted of 1,643 adolescents (822 girls, 821 boys). Motivational variables consisted of PA enjoyment, self-efficacy, and peer social support. Mediator variables consisted of segmented weekly PA and SB assessed using the Youth Activity Profile (YAP). BMI% was the outcome. A recursive bootstrapped path analysis was conducted to examine the relationships between motivational variables, segmented PA and SB, and BMI% with indirect effects calculated via bootstrapped mediation analyses. Results: The relationships between motivational variables and segmented PA and SB were stronger than relationships between segmented PA and SB and BMI%. Three mediated paths were observed: self-efficacy and BMI% using sedentary YAP as the mediator (IE = -0.38, 95%CI: -0.65, -0.18), enjoyment and BMI% using weekend YAP as the mediator (IE = -0.62, 95%CI: -1.14, -0.12) and social support and BMI% using weekend YAP as the mediator (IE = -0.53, 95%CI: -1.00, -0.07). Conclusion: The relationship between adolescent motivational variables and segmented PA and SB is relatively strong and specific motivational variables' relationships with BMI% is mediated through segmented PA and SB.

Stress of life events and anxiety as mediators of the association between insomnia and triglycerides in college students.

Purpose: This study examined interrelationships among insomnia, stress, anxiety, and metabolic risk factors. Methods: A total of 124 college students were included in the analysis (age = 21 ± 1 years). Insomnia, stress of life events, and anxiety were assessed using self-reported questionnaires. Fasting blood samples were assayed for glucose, insulin, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-cholesterol), and low-density lipoprotein cholesterol (LDL-cholesterol). Results: Insomnia was positively associated with stress of life events (ß = 0.28, p < .001) and anxiety (ß = 0.46, p < .001). Insomnia was related to elevated fasting insulin (ß = 0.12, p = .04) and triglyceride level (ß = 1.85, p < .001). An inverse association was found between insomnia and HDL-cholesterol (ß = -0.45, p = .03). Sobel's test for mediation showed that stress of life events (p = .020) and anxiety (p = .013) mediated the relationship between insomnia and hypertriglyceridemia. Conclusions: Reducing stress and anxiety among college students with insomnia may influence subsequent cardiovascular health.

Fear of falling avoidance behavior affects the inter-relationship between vision impairment and diminished mobility in community-dwelling older adults.

BACKGROUND: Age-related decline in vision may contribute to the development of fear of falling (FOF) behavior and reduced mobility, which are related to increased fall risk in older adults. PURPOSE: To investigate the inter-relationship between vision impairment, physical mobility performance, and FOF behavior in community-dwelling older adults. METHODS: A total of 400 participants from community centers (267 females; age = 74.8 (6.4), range = 65-97 years) participated in this cross-sectional study. Presence of age-related eye diseases (e.g. macular degeneration, cataracts, glaucoma, and retinopathy) and visual acuity (VA) was assessed. Physical mobility and FOF avoidance behavior were assessed using the Timed Up-and-Go (TUG) test and the Fear of Falling Avoidance Behavior Questionnaire (FFABQ). The inter-relationships between parameters were analyzed using mediation model analysis. RESULTS: Significant decreases in mobility performance were observed in those with eye disease (eye disease = 9.56 [5.2] sec, no eye disease = 8.54 [2.75] sec; p = .037) and FOF avoidance behavior (avoiders = 12.87 [6.04] sec, non-avoiders = 8.51 [3.56] sec; p < .001). Furthermore, FOF behavior was found to significantly influence the inter-relationship between presence of eye disease and TUG performance (p = .004). VA alone had no significant effect on mobility (p = .69). CONCLUSION: The presence of eye disease and the associated FOF behavior was related to decreased mobility and potentially increased fall risk. We recommend clinicians to inquire about the presence of eye disease and FOF behavior to identify risk factors related to falls in older adults.

Monascin and Ankaflavin of Monascus purpureus Prevent Alcoholic Liver Disease through Regulating AMPK-Mediated Lipid Metabolism and Enhancing Both Anti-Inflammatory and Anti-Oxidative Systems.

Alcohol metabolism causes an excessive accumulation of liver lipids and inflammation, resulting in liver damage. The yellow pigments monascin (MS) and ankaflavin (AK) of Monascus purpureus-fermented rice were proven to regulate ethanol-induced damage in HepG2 cells, but the complete anti-inflammatory and anti-fatty liver mechanisms in the animal model are still unclear. This study explored the roles of MS and AK in improving alcoholic liver injury. MS and AK were simultaneously fed to evaluate their effects and mechanisms in C57BL/6J mice fed the Lieber-DeCarli liquid alcohol diet for 6 weeks. The results indicated that MS and AK significantly reduced the serum aspartate aminotransferase and alanine aminotransferase activity, as well as the total liver cholesterol and triglyceride levels. The histopathological results indicated that MS and AK prevented lipid accumulation in the liver. MS and AK effectively enhanced the activity of antioxidant enzymes and reduced the degree of lipid peroxidation; AK was particularly effective and exhibited a superior preventive effect against alcoholic liver injury and fatty liver. In addition to inhibiting the phosphorylation of the MAPK family, MS and AK directly reduced TNF-α, IL-6, and IL-1ß levels, thereby reducing NF-κB and its downstream iNOS and COX-2 expressions, as well as increasing PPAR-γ, Nrf-2, and HO-1 expressions to prevent liver damage. MS and AK also directly reduced TNF-α, IL-6, and IL-1ß expression, thereby reducing the production of NF-κB and its downstream iNOS and COX-2, and increasing PPAR-γ, Nrf-2, and HO-1 expressions, preventing alcohol damage to the liver.

EMP2 induces cytostasis and apoptosis via the TGFß/SMAD/SP1 axis and recruitment of P2RX7 in urinary bladder urothelial carcinoma.

PURPOSE: Urinary bladder urothelial carcinoma (UBUC) is a common malignant disease, and its high recurrence rates impose a heavy clinical burden. The objective of this study was to identify signaling pathways downstream of epithelial membrane protein 2 (EMP2), which induces cytostasis and apoptosis in UBUC. METHODS: A series of in vitro and in vivo assays using different UBUC-derived cell lines and mouse xenograft models were performed, respectively. In addition, primary UBUC specimens were evaluated by immunohistochemistry. RESULTS: Exogenous expression of EMP2 in J82 UBUC cells significantly decreased DNA replication and altered the expression levels of several TGFß signaling-related proteins. EMP2 knockdown in BFTC905 UBUC cells resulted in opposite effects. EMP2-dysregulated cell cycle progression was found to be mediated by the TGFß/TGFBR1/SP1 family member SMAD. EMP2 or purinergic receptor P2X7 (P2RX7) gene expression upregulation induced apoptosis via both intrinsic and extrinsic pathways. In 242 UBUC patient samples, P2RX7 protein levels were found to be significantly and positively correlated with EMP2 protein levels. Low P2RX7 levels conferred poor disease-specific and metastasis-free survival rates, and significantly decreased apoptotic cell rates. EMP2 was found to physically interact with P2RX7. In the presence of a P2RX7 agonist, BzATP, overexpression of both EMP2 and P2RX7 significantly increased apoptotic cell rates compared to overexpression of EMP2 or P2RX7 alone. CONCLUSIONS: EMP2 induces cytostasis via the TGFß/SMAD/SP1 axis and recruits P2RX7 to enhance apoptosis in UBUC. Our data provide new insights that may be employed for the design of UBUC targeting therapies.

Socio-Ecological Predictors of Frequent Bike Share Trips: Do Purposes Matter?

Using bike share could increase physical activity and improve health. This study used the social-ecological model to identify predictors of frequent bike share trips for different purposes. Participants residing in the U.S. were recruited via Amazon Mechanical Turk (MTurk). Self-report trip purposes were used to group participants into using bike share for commuting only (n = 260), social/entertainment only (n = 313), exercise only (n = 358), dual or triple-purpose (n = 501), and purposes other than commuting, social/entertainment, and exercise (n = 279). Results showed that at the intrapersonal level, perceived use of bike share to be helpful for increasing physical activity was a significant predictor for all groups, except for the other purpose group. Adjusting outdoor activity based on air quality was a significant predictor for the dual or triple-purpose group. At the interpersonal level, having four or more friends/family using bike share was a significant predictor for the other purpose group. At the community level, distance to the nearest bike share within acceptable range was a significant predictor for social/entertainment and dual or triple-purpose groups. The findings suggest that it is important to consider factors at multiple levels for predicting bike share usage. Moreover, health educators and policy makers should adopt different strategies for promoting bike share usage based on trip purposes.

A Pilot Study of Hip Corrective Taping Using Kinesio Tape for Pain and Lower Extremity Joint Kinematics in Basketball Players with Patellofemoral Pain.

PURPOSE: This pilot study aimed to determine the feasibility of hip corrective taping to improve self-reported knee pain and lower extremity joint kinematics in basketball players with patellofemoral pain. PATIENTS AND METHODS: A single group pre-test and post-test design. Collegiate basketball players with patellofemoral pain were recruited. Three-dimensional hip and knee joint kinematics were measured during two tasks, single-leg squat (SLS) and lay-up jump (LUJ), and each task was conducted under no-taping and taping conditions. Subjective report of pain was compared between no-taping and taping conditions only during SLS. RESULTS: Twelve collegiate basketball players with patellofemoral pain (median age, 22.7 [2.5] years; mean height, 173.8 ± 7.4 cm; mean weight, 72.5 ± 12.8 kg) participated in this study. Compared with no-taping, the use of hip corrective taping significantly increased the hip abduction angle at the instant of the maximal vertical ground reaction force during LUJ (no-taping vs taping: 0.6° ± 6.3° vs 3.3° ± 5.1°, p = 0.029), and also caused a trend of decreased maximal hip internal rotation angle during SLS (no-taping vs taping: 8.0° ± 6.6° vs 4.7° ± 6.9°, p = 0.050). Hip corrective taping also improved self-reported knee pain during SLS (no-taping vs taping: 3.4 ± 1.7 vs 2.6 ± 1.0, p = 0.046). CONCLUSION: Hip corrective taping may be used as an effective intervention for athletes with patellofemoral pain during basketball-related tasks.

Estimation of the Number of Passengers in a Bus Using Deep Learning.

For the development of intelligent transportation systems, if real-time information on the number of people on buses can be obtained, it will not only help transport operators to schedule buses but also improve the convenience for passengers to schedule their travel times accordingly. This study proposes a method for estimating the number of passengers on a bus. The method is based on deep learning to estimate passenger occupancy in different scenarios. Two deep learning methods are used to accomplish this: the first is a convolutional autoencoder, mainly used to extract features from crowds of passengers and to determine the number of people in a crowd; the second is the you only look once version 3 architecture, mainly for detecting the area in which head features are clearer on a bus. The results obtained by the two methods are summed to calculate the current passenger occupancy rate of the bus. To demonstrate the algorithmic performance, experiments for estimating the number of passengers at different bus times and bus stops were performed. The results indicate that the proposed system performs better than some existing methods.

Mitochondrial Heat Shock Protein 60s Interact with What's This Factor 9 to Regulate RNA Splicing of ccmFC and rpl2.

Mitochondrial intron splicing is a plant-specific feature that was acquired during the co-evolution of eukaryotic host cells and a-proteobacteria. The elimination of these introns is facilitated by mitochondrial-targeted proteins encoded by its host, nucleus. What's this factor 9 (WTF9), a nuclear-encoded plant organelle RNA recognition (PORR) protein, is involved in the splicing of the mitochondrial group II introns rpl2 and ccmFC. Disruption of WTF9 causes developmental defects associated with the loss of Cyt c and Cyt c1 in Arabidopsis. In the present study, using a co-immunoprecipitation assay, we found that HSP60s interacted with WTF9, which was further confirmed by a pull-down assay. HSP60s are molecular chaperones that assist with protein folding in both eukaryotic and prokaryotic cells. However, accumulating evidence suggests that HSP60s also participate in other biological functions such as RNA metabolism and RNA protection. In this study, we found that consistently with their interaction with WTF9, HSP60s interacted with 48 nucleotides of the ccmFC intron. In mutant studies, the double mutant hsp60-3a1hsp60-3b1 exhibited a small stature phenotype and reduced splicing efficiency for rpl2 and ccmFC. These observations were similar to those in wtf9 mutants and suggest that HSP60s are involved in the RNA splicing of rpl2 and ccmFC introns in mitochondria. Our findings suggest that HSP60s participate in mitochondrial RNA splicing through their RNA-binding ability.

Collegiate baseball players with more optimal functional movement patterns demonstrate better athletic performance in speed and agility.

Sports injuries are common among baseball players and may result in abnormal movement patterns, increased risks of future injury, and unsatisfactory performance. The Functional Movement Screen (FMS™) has been developed to detect abnormal functional movement patterns and can be used for predicting risks of sports injury. However, whether FMS™ scores are associated with athletic performance remains unclear. The goal of this study was to determine the association between functional movements and athletic performance in elite baseball players. Core stability, muscular strength and flexibility of the lower extremities, and FMS™, as well as athletic performance in sprinting, agility, and balance tests were assessed in 52 male collegiate Division I baseball players placed into two groups based on FMS™ scores. The high-scoring group demonstrated better athletic performance than the low-scoring group, with a shorter duration of the agility test. No group differences were found in core stability, muscular strength, or muscle flexibility, except for rectus femoris flexibility. Thus, the FMS™ score is associated with sprinting and agility performance in elite baseball players. These findings indicate that the FMS™ may have a role in predicting athletic performance and thereby help determine the goals of training regimens or return-to-play strategies.

Measuring Athletic Mental Energy (AME): Instrument Development and Validation.

Although considerable research indicates that mental energy is an important factor in many domains, including athletic performance (Cook and Davis, 2006), athletic mental energy (AME) has never been conceptualized and measured. Therefore, the aim of this study was to conceptualize and develop a reliable and valid instrument to assess AME. In Study 1, a focus group interview established the initial framework of AME. Study 2 used a survey to collect athletes' experiences of AME and develop a scale draft titled "Athletic Mental Energy Scale (AMES)." In Study 3, we examined the psychometric properties and the underlying structure of AMES via item analysis, internal consistency, and exploratory factor analysis (EFA). In Study 4, we used confirmatory factor analysis (CFA) to examine AMES's factorial validity; and examined concurrent and discriminant validity by examining correlations with athletes' life stress, positive state of mind, and burnout. In study 5, we examined the measurement invariance of the 6-factor, 18-item AMES with Taiwanese and Malaysian samples. Study 6 examined the predictive validity by comparing AMES scores of successful and unsuccessful martial artists. Across these phases, results showed a 6-factor, 18-item AMES had adequate content validity, factorial structure, nomological validity, discriminant validity, predictive validity, measurement invariance, and reliability. We suggest future studies may use AMES to examine its relationships with athletes' cognition, affect, and performance. The application of AMES in sport psychology was also discussed.

Prediction of life stress on athletes' burnout: the dual role of perceived stress.

Although many studies adopted Smith's (1986) cognitive-affective model of athletic burnout in examining stress-burnout relationship, very few studies examined the mediating/moderating role of perceived stress on the stress-burnout relationship. We sampled 195 college student-athletes and assessed their life stress, perceived stress, and burnout. Correlation analyses found all study variables correlated. Two separate hierarchical regression analyses found that the "distress" component of perceived stress mediated athletes' two types of life stress-burnout relationship but "counter-stress" component of perceived stress-moderated athletes' general-life stress-burnout relationship. We concluded that interweaving relationships among athletes' life stress, perceived stress, and burnout are not straightforward. Future research should consider the nature of athletes life stress, and dual role of perceived stress in examining its' association with related psychological responses in athletic settings.

The blood lipid regulation of Monascus-produced monascin and ankaflavin via the suppression of low-density lipoprotein cholesterol assembly and stimulation of apolipoprotein A1 expression in the liver.

BACKGROUND/PURPOSES: Monascin (MS) and ankaflavin (AK) produced by Monascus purpureus NTU 568 were proven to show excellent hypolipidemic effects in our previous studies; however, the mechanism is still unclear. METHODS: This study used MS, AK, and monacolin K as test substances and performed tests on rats fed high-fat and high-cholesterol diet for 8 weeks. The lipid levels and the related protein levels of the rats were assessed to understand the effects of MS, AK, and monacolin K on lipid metabolism. RESULTS: MS and AK lowered low-density lipoprotein cholesterol (LDL-C) and preserved high-density lipoprotein cholesterol contents. MS and AK inhibited acetyl-coenzyme A acetyltransferase, microsomal triglyceride transfer protein, and apolipoprotein (apo) B-100 expression, thereby preventing LDL assembly. In addition, enhanced LDL-receptor expression increased the transport of LDL-C to the liver for metabolism. MS and AK also significantly increase apo A1 expression, which facilitates high-density lipoprotein cholesterol formation. CONCLUSION: Monascus-fermented MS and AK can perform blood lipid regulation via the suppression of LDL-C assembly and stimulation of apo A1 expression in liver.

The Influence of Parental Education on Dietary Intake in Latino Youth.

Acculturation to the US culture is associated with suboptimal dietary choices in Latino youth. The role of parental education in shaping children's nutrition is less clear. The purpose of this study was to examine the relationships between parental education, acculturation and dietary intake in 96 Latino youth ages 8-18 years. Parental education was assessed using a seven-category variable. Acculturation was assessed using the Acculturation, Habits, and Interests Multicultural Scale for Adolescents questionnaire. Dietary intake was assessed via 24-h dietary recalls using the multiple pass technique. Parental education was associated with lower fat intake (ß = -0.115, p = 0.02) and lower fiber intake (ß = 0.144, p = 0.03); these associations remained significant after controlling for age, sex, BMI and acculturation. There were no significant associations between acculturation and dietary variables (all p's >0.05). This data suggests parental education may play an important role in shaping dietary intake in Latino youth.

Increased risk of chronic kidney disease in patients with rosacea: A nationwide population-based matched cohort study.

BACKGROUND: Rosacea is a chronic inflammatory skin disorder. Inflammation and oxidative stress are involved in the etiopathogenesis of rosacea and chronic kidney disease (CKD). This study aimed to investigate the association between rosacea and CKD. METHODS: This population-based cohort study identified 277 patients with rosacea in the Taiwan National Health Insurance Research Database during 2001-2005. These patients were matched for age, sex, and comorbidities with 2216 patients without rosacea. All subjects were individually followed-up for 8-12 years to identify those who subsequently developed CKD. RESULTS: The incidence rates of CKD per 1000 person-years were 16.02 in patients with rosacea and 10.63 in the non-rosacea reference population. After adjusting for other covariates and considering the competing risk of mortality, patients with rosacea remained at increased risk of CKD (adjusted sub-distribution hazard ratio (aSD-HR) 2.00; 95% confidence interval (CI) 1.05-3.82). The aSD-HRs (95% CI) for CKD were 1.82 (0.83-4.00) and 2.53 (1.11-5.75) for patients with mild and moderate-to-severe rosacea, respectively. CONCLUSIONS: Rosacea is an independent risk factor for CKD. High rosacea severity and old age further increased CKD risk in patients with rosacea. Careful monitoring for CKD development should be included as part of integrated care for patients with rosacea.

Relapse insomnia increases greater risk of anxiety and depression: evidence from a population-based 4-year cohort study.

OBJECTIVE: We investigated the longitudinal impacts of insomnia on the subsequent developments of anxiety and depression during a four-year follow-up. We further categorized individuals with insomnia into different insomnia subgroups to examine whether the risk of anxiety and depression varies by subtype. METHODS: Participants were identified from National Health Insurance enrollees in Taiwan during 2002-2009. The study included 19,273 subjects with insomnia and 38,546 matched subjects without insomnia. All subjects did not have previous diagnosis of insomnia, sleep apnea, anxiety, or depression. RESULTS: Compared with non-insomniacs, insomniacs had a higher risk of developing anxiety only [adjusted hazard ratio (HR) = 8.83, 95% CI = 7.59-10.27], depression only (adjusted HR = 8.48, 95% CI = 6.92-10.39), and both anxiety and depression (adjusted HR = 17.98, 95% CI = 12.65-25.56). When breaking down the insomnia subgroups, individuals with a relapse of insomnia (adjusted HR = 10.42-26.80) had the highest risk of anxiety only, depression only, and both anxiety and depression, followed by persistent insomnia (adjusted HR = 9.82-18.98), then remitted insomnia (adjusted HR = 4.50-8.27). All three insomnia subgroups had a greater four-year cumulative incidence rate than the non-insomnia group for anxiety only, depression only, and both anxiety and depression (p < 0.0001). CONCLUSION: Our findings reinforce the clinical predictor role of insomnia in the future onset of anxiety or/and depression. Awareness of insomnia and treatment of insomnia should be recommended at clinics, and patterns of insomnia should be monitored to help treatment and control of subsequent psychiatric disorders. Future research with comprehensive data collection is needed to identify factors that contribute to different insomnia subtypes.

Novel histone deacetylase inhibitor AR-42 exhibits antitumor activity in pancreatic cancer cells by affecting multiple biochemical pathways.

OBJECTIVE: Pancreatic cancer is one of the most lethal types of cancer with a 5-year survival rate of ~5%. Histone deacetylases (HDACs) participate in many cellular processes, including carcinogenesis, and pharmacological inhibition of HDACs has emerged as a potential therapeutic strategy. In this study, we explored antitumor activity of the novel HDAC inhibitor AR-42 in pancreatic cancer. METHODS: Human pancreatic cancer cell lines BxPC-3 and PANC-1 were used in this study. Real-time PCR, RT-PCR, and western blotting were employed to investigate expression of specific genes and proteins, respectively. Translocation of apoptosis-inducing factor was investigated by immunofluorescence and subcellular fractionation. The number of apoptotic cells, cell cycle stages, and reactive oxygen species (ROS) generation levels were determined by flow cytometry. Cell invasiveness was examined by the Matrigel invasion assay. Efficacy of AR-42 in vivo was evaluated by utilizing BxPC-3 xenograft mouse model. RESULTS: AR-42 inhibited pancreatic cancer cell proliferation by causing G2/M cell cycle arrest via regulating expression levels of genes and proteins involved in cell cycle. AR-42 also induced ROS generation and DNA damage, triggering apoptosis of pancreatic cancer cells via both caspase-3-dependent and caspase-3-independent pathways. In addition, AR-42 increased expression levels of negative regulators of p53 (miR-125b, miR-30d, and miR33), which could contribute to lower expression level of mutant p53 in pancreatic cancer cells. Cell invasion assay showed that AR-42 reduced cancer cell aggressiveness and significantly diminished BxPC-3 xenograft tumor growth in vivo. CONCLUSION: AR-42, a novel HDAC inhibitor, inhibited pancreatic cancer cells by regulating p53 expression, inducing cell cycle arrest, particularly at the G2/M stage, and activating multiple apoptosis pathways. Additionally, AR-42 inhibited cell invasiveness and potently suppressed pancreatic cancer tumors in vivo. We conclude that by virtue of its multiple mechanisms of action, AR-42 possesses a considerable potential as an antitumor agent in pancreatic cancer.

Comparison of healthcare utilization and life-sustaining interventions between elderly patients with dementia and those with cancer near the end of life: A nationwide, population-based study in Taiwan.

AIM: Little is known about the pattern of healthcare services for end-of-life patients with dementia (PwD) in East Asia. We compared this pattern between PwD and cancer patients in their last year of life in Taiwan. METHODS: Taiwan's National Health Insurance Research Database was applied for this case-control analysis. The records of patients who had dementia and died between 2002 and 2011 were reviewed. The control group was decedents with cancer. The utilization of hospitalization, emergency department visits and life-sustaining interventions during the last year of life between the two groups were compared. RESULTS: Of the 2724 patients enrolled, 908 had dementia and 1816 had cancer. PwD were more likely to have a higher frequency of admission to hospital and intensive care unit, and longer stays compared with cancer patients. PwD had a higher risk of enteral tube insertion and feeding, endotracheal intubation and tracheostomy, mechanical ventilation, hemodialysis and cardiopulmonary resuscitation (OR 4.36, 95% CI 3.51-5.41), which was the highest among the selected procedures. CONCLUSIONS: PwD in their last year of life in Taiwan underwent aggressive interventions significantly more frequently than did their counterparts in Western countries. Providing comfort-centered care for better quality of life for end-of-life PwD is a priority of Taiwan's national health policy. Geriatr Gerontol Int 2017; 17: 2545-2551.