Occupational physical activity, all-cause, cardiovascular disease, and cancer mortality in 349,248 adults: Prospective and longitudinal analyses of the MJ Cohort.

BACKGROUND: Evidence on the health benefits of occupational physical activity (OPA) is inconclusive. We examined the associations of baseline OPA and OPA changes with all-cause, cardiovascular disease (CVD), and cancer mortality and survival times. METHODS: This study included prospective and longitudinal data from the MJ Cohort, comprising adults over 18 years recruited in 1998-2016, 349,248 adults (177,314 women) with baseline OPA, of whom 105,715 (52,503 women) had 2 OPA measures at 6.3 ± 4.2 years (mean ± SD) apart. Exposures were baseline OPA, OPA changes, and baseline leisure-time physical activity. RESULTS: Over a mean mortality follow-up of 16.2 ± 5.5 years for men and 16.4 ± 5.4 years for women, 11,696 deaths (2033 of CVD and 4631 of cancer causes) in men and 8980 deaths (1475 of CVD and 3689 of cancer causes) in women occurred. Combined moderately heavy/heavy baseline OPA was beneficially associated with all-cause mortality in men (multivariable-adjusted hazard ratio (HR) = 0.93, 95% confidence interval (95%CI): 0.89-0.98 compared to light OPA) and women (HR = 0.86, 95%CI: 0.79-0.93). Over a mean mortality follow-up of 12.5 ± 4.6 years for men and 12.6 ± 4.6 years for women, OPA decreases in men were detrimentally associated (HR = 1.16, 95%CI: 1.01-1.33) with all-cause mortality, while OPA increases in women were beneficially (HR = 0.83, 95%CI: 0.70-0.97) associated with the same outcome. Baseline or changes in OPA showed no associations with CVD or cancer mortality. CONCLUSION: Higher baseline OPA was beneficially associated with all-cause mortality risk in both men and women. Our longitudinal OPA analyses partly confirmed the prospective findings, with some discordance between sex groups.

Social isolation and cognitive function in patients with schizophrenia: A two years follow-up study.

Cognitive impairment is a core characteristic of schizophrenia. Social isolation has been linked to impaired cognitive function among the general population. In this longitudinal study, we examined the association between social isolation and cognitive function among inpatients with schizophrenia. Two waves of data (2019 and 2021) were collected from chronic psychiatric wards. A total of 166 inpatients completed all measurements at baseline and follow-up. Social isolation was measured by incorporating the frequency of social contact and participation, while cognitive functions were assessed by the Taiwan version of the Montreal Cognitive Assessment (MoCA-T). We used multiple linear regression to evaluate the link between baseline social isolation and cognitive function. For the total sample, social isolation was significantly related to poor language abilities (ß = -0.17, p = 0.013) and delayed recall (ß = -0.15, p = 0.023). Sex-stratified analysis showed that social isolation was significantly related to poor global cognitive function (ß = -0.14, p = 0.021) and domain-specific cognitive functions including language abilities (ß = -0.26, p = 0.003) and delayed recall (ß = -0.19, p = 0.045) in male inpatients. No significant association was found between social isolation and global cognitive function or any cognitive domain (all ps > 0.05) for females. All associations were independent of loneliness and other covariates. These findings suggested that social isolation could predict poor subsequent cognitive function in inpatients with schizophrenia, especially in males. Interventions aimed at enhancing social connections could potentially improve cognitive function in this population.

Modification of incident cancer risk with changes in metabolic syndrome status: A prospective cohort study in Taiwan.

PURPOSE: We aimed to investigate the effect of altered metabolic syndrome (MetS) status on cancer risk. METHODS: From 2002 through 2008 of the Taiwan MJ cohort, there were 111,616 adults who had repeated MetS measurements performed 3.3 years apart and were followed up for cancer incidence over 11.8 years. Cancer was confirmed based on histopathological reports. RESULTS: Participants were categorized as MetS-free (n = 80,409; no MetS at the first or last health screening), MetS-developed (n = 9833; MetS absence at the first screening and presence at the last screening), MetS-recovered (n = 8958; MetS presence at the first screening and absence at the last screening), and MetS-persisted (n = 12,416; MetS presence at the first and last screenings). We used the Fine-Gray sub-distribution method, with death as competing risk, to determine the association between MetS changes and incident cancer risk. During 1320,796 person-years of follow-up, 5862 individuals developed cancer. The incidence rate of cancer per 1000 person-years was 3.89 in the MetS-free, 5.26 in MetS-developed, 4.61 in MetS-recovered, and 7.33 in MetS-persisted groups (P < .001). Compared with the MetS-free group, MetS-persisted individuals had a higher risk of incident cancer. CONCLUSIONS: Persistent MetS was found to be associated with a high risk of incident cancer.

Effect of a Single Light-intensity Walking Session on Sleep Quality of Patients with Bladder Cancer: A Randomized Cross-Over Study.

OBJECTIVES: Exercise has been recommended to enhance sleep. However, there is a paucity of studies investigating the relationships between exercise and sleep problems in patients with bladder cancer. The authors explored the effects of a single bout of light-intensity walking on the sleep quality of patients with bladder cancer who have sleep disorders. DATA SOURCES: A total of 14 patients with bladder cancer with sleep disorders were recruited for this trial. The participants were randomly assigned to the walking or control condition in a cross-over design to explore the effects of a single light-intensity walking session on objectively measured sleep quality. A two-way repeated measures analysis of variance and a nonparametric permutation test were used to examine intervention effects. Twelve participants (85.7%) completed the trial. A significant group × time interaction for sleep latency (P = .023) was identified. The pairwise comparison showed significant results (P = .012) for the difference between the post-test sleep latency and the pre-test. No significant group × time interactions were observed for the remaining seven sleep parameters. Additionally, only the main effects of time on length of awakening and time in bed were significant (P < .001). CONCLUSION: A single bout of light-intensity walking has a positive effect on shortening the sleep latency of patients with bladder cancer who have sleep disorders. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses can encourage patients with bladder cancer to exercise, even light-intensity walking, which may improve sleep quality.

Continuous nerve block versus thoracic epidural analgesia for post-operative pain of pectus excavatum repair: a systematic review and meta-analysis.

Surgery to repair pectus excavatum (PE) is often associated with severe postoperative pain, which can impact the length of hospital stay (LOS). While thoracic epidural analgesia (TEA) has traditionally been used for pain management in PE, its placement can sometimes result in severe neurological complications. Recently, paravertebral block (PVB) and erector spinae plane block (ESPB) have been recommended for many other chest and abdominal surgeries. However, due to the more severe and prolonged pain associated with PE repair, it is still unclear whether continuous administration of these blocks is as effective as TEA. Therefore, we conducted this systematic review and meta-analysis to demonstrate the equivalence of continuous PVB and ESPB to TEA.

The effect of physical activity on sleep disturbance in various populations: a scoping review of randomized clinical trials.

BACKGROUND: Promoting physical activity (PA) in different populations experiencing sleep disturbance may increase population PA levels and improve sleep. This scoping review aimed to examine the effect of various PA intervention strategies on sleep across different populations, identify key sleep outcomes, and analyze knowledge gaps by mapping the relevant literature. METHODS: For this study, we systematically searched articles published till March 2022 from PubMed, Web of Science, Cochrane Library, and Embase databases for randomized clinical trials (RCTs) regarding the effect of physical activity on sleep. Two authors extracted key data and descriptively analyzed the data. Thematic analysis was used to categorize the results into themes by all authors. Arksey and O'Malley's scoping review framework was used to present the findings. RESULTS: Twenty-one randomized controlled trials out of 3052 studies were finally included with 3677 participants (2852 females (78%)). Five trials were conducted in healthy working-age adults with sleep disturbance but without the diagnosis of insomnia, five in healthy older adults, two in perinatal women, four in patients with cancer, three in mental illness related subjects, and another two in other disease-related areas. PA interventions were diverse, including walking, resistance training, aerobic exercise, housework, water exercise, basketball, smartphone/tablet "apps", web, online videos or wearable actigraphy, and self-determined exercise. Three major themes were identified: (1) Sleep environment may be important to address prior to instituting PA interventions, (2) All types of PA were effective for improving sleep in all populations studied, (3) Self-tolerated PA is safe for improving sleep in the elderly and in co-morbid or perinatal populations. CONCLUSIONS: PA is effective and safe for improving sleep in both healthy and co-morbid populations with sleep disturbance by increasing daily activity levels using a variety of strategies, even low intensity, such as housekeeping, sit-to-stand repetitions, along with encouraging PA through web pages, videos, and self-goal setting apps. In addition, this scoping review identifies the need for further therapeutic research and future exploration in populations with sleep initiation or sleep maintenance disturbance.

Changes in physical activity and adiposity with all-cause, cardiovascular disease, and cancer mortality.

BACKGROUND: The relationship between joint changes in physical activity and adiposity with mortality is not well understood. We examined the association of changes in these two established risk factors with all-cause (ACM), cardiovascular disease (CVD), and cancer mortality. METHODS: We used longitudinal data from Taiwan's MJ Cohort, comprising 116,228 general population adults recruited from 1998-2013 with repeated measures 4.6 y (2.5) apart and followed up for mortality for 11.9 y (3.5). Physical activity, body mass index (BMI), waist circumference (WC), and body fat percentage (BF%) groups and changes were based on public health and clinical guidelines. RESULTS: Compared to stable-insufficient physical activity, increasing physical activity from any baseline level was associated with lower ACM (HR [95%CI]): 0.85 [0.74, 0.96]) and CVD mortality (0.72 [0.55, 0.93]) risk. This was approximately equal to meeting physical activity guidelines at both timepoints (eg: 0.71 [0.58, 0.88] for CVD mortality). Compared to stable-overweight/moderate adiposity, decreasing adiposity level attenuated but did not offset mortality risk for all three outcomes (eg: BMI = 0.95 [0.76, 1.16] for CVD mortality). Only maintaining a healthy adiposity level at both timepoints offset mortality risk (BMI = 0.75 [0.61, 0.89]) for CVD mortality). In the joint changes analyses, lower mortality risk was a consequence of increases in physical activity across adiposity change groups (eg: WC decrease = 0.57 [0.48, 0.67]; WC stability = 0.73 [0.66, 0.80], WC increase = 0.83 [0.72, 0.97] for ACM). Decreasing adiposity attenuated the negative associations of decreased physical activity (BF% = 1.13 [0.95, 1.35] for ACM). CONCLUSIONS: We found a lower risk for ACM, CVD, and cancer mortality from increasing physical activity and an attenuation from decreasing adiposity regardless of baseline levels. The beneficial associations of joint changes were primarily driven by physical activity, suggesting lower mortality risk may be more immediate through physical activity improvements compared to adiposity improvements alone.

Hospice Care Services Associated With a Lower Utilization of Life-Sustaining Treatments During End-Of-Life Care Among People Living With HIV/AIDS: A Population-Based Cohort Study.

Background: Hospice care involves improving quality of end-of-life (EOL) care and respecting patients' preferences regarding EOL treatment. However, the impact of hospice care services on the utilization of life-sustaining treatments during EOL care in patients with life-limiting diseases has not been extensively studied. Objectives: This nationwide cohort study aimed to determine the impact of hospice care services on the utilization of life-sustaining treatments during the last 3 months of life among people living with HIV/AIDS (PLWHA) in Taiwan. Methods: From 2000 to 2018, we identified adult PLWHA from Taiwan centers for disease control HIV Surveillance System. HIV-infected individuals were defined as positive HIV-1 Western blot. Life-sustaining treatments included cardiopulmonary resuscitation, intubation, mechanical ventilation support, and defibrillation. The association of hospice care services with the utilization of life-sustaining treatments was determined using multiple logistic regression. Results: Of 5691 PLWHA, 2595 (45.9%) subjects utilized life-sustaining treatments during the last 3 months of life. After adjusting for other covariates, PLWHA with hospice care services were less likely to receive life-sustaining treatments during the last 3 months of life than those without the services (adjusted odds ratio [AOR] = .50, 95% confidence interval [CI]: .37-.66). Considering the type of life-sustaining treatments, hospice care services were associated with lower likelihood of receiving cardiopulmonary resuscitation (AOR = .22, 95% CI: .13-.39), endotracheal intubation (AOR = .48, 95% CI: .35-.65), and mechanical ventilation support (AOR = .56, 95% CI: .42-.75). Conclusion: Hospice care services were associated with a lower utilization of life-sustaining treatments during the last 3 months of life among PLWHA.

Can physical activity eliminate the mortality risk associated with poor sleep? A 15-year follow-up of 341,248 MJ Cohort participants.

BACKGROUND: This study examined the joint associations of sleep patterns and physical activity (PA) with all-cause, cardiovascular disease (CVD), and cancer mortality. METHODS: A total of 341,248 adults (mean age = 39.7 years; men: 48.3%) were included in the study, with a 15-year follow-up. Participants reported sleep duration and disturbances (difficulty falling asleep, easily awakened, or use of sleeping medication). PA was classified into 4 levels: <7.5, 7.5-14.9, 15.0-29.9, and ≥30.0 metabolic equivalent hours per week (MET-h/week). To understand the joint associations of sleep patterns and PA with mortality, Cox proportional hazard models were conducted, with exposure variables combining sleep duration/disturbances and PA. RESULTS: Compared with the reference group (sleeping 6-8 h/day), individuals who slept >8 h/day had higher risk for all-cause mortality (hazard ratio (HR) = 1.307, 95% confidence interval (95%CI): 1.248-1.369), CVD mortality (HR = 1.298, 95%CI: 1.165-1.445), and cancer mortality (HR = 1.128, 95%CI: 1.042-1.220). Short sleep duration was not associated with mortality risk. Increased risk of all-cause and CVD mortality was found in participants who had difficulty falling asleep (HR = 1.120, 95%CI: 1.068-1.175; HR = 1.163, 95%CI: 1.038-1.304, respectively), and used sleeping medication (HR = 1.261, 95%CI: 1.159-1.372; HR = 1.335, 95%CI: 1.102-1.618, respectively) compared with those who slept well. Long sleep duration and sleep disturbances were not associated with risk of all-cause and CVD mortality among individuals achieving a PA level of ≥15 MET-h/week, and in particular among those achieving ≥30 MET-h/week. CONCLUSION: Long sleep duration, difficulty falling asleep, and use of sleeping medication were related to a higher risk of death. Being physically active at a moderate intensity for 25-65 min/day eliminated these detrimental associations.

Nicotine supplementation enhances simulated game performance of archery athletes.

BACKGROUND: Nicotine is beneficial to mood, arousal and cognition in humans. Due to the importance of cognitive functioning for archery athletes, we investigated the effects of nicotine supplementation on the cognitive abilities, heart rate variability (HRV), and sport performance of professional archers. METHODS: Eleven college archers were recruited and given 2 mg of nicotine supplementation (NIC group) and placebo (PLA group) in a crossover design. RESULTS: The results showed that at 30 min after the intake of nicotine gum, the "correct rejection" time in the NIC group was significantly lower than that of the PLA group (7.29 ± 0.87 vs. 8.23 ± 0.98 msec, p < 0.05). In addition, the NIC group completed the grooved pegboard test in a shorter time than the PLA group (48.76 ± 3.18 vs. 53.41 ± 4.05 s, p < 0.05), whereas motor reaction times were not different between the two groups. Saliva α-amylase activity was significantly lower after nicotine supplementation (p < 0.01) but increased immediately after the archery test in the NIC group (p < 0.05). In addition, nicotine supplementation significantly decreased HRV and increased the archery score (290.58 ± 10.09 vs. 298.05 ± 8.56, p < 0.01). CONCLUSIONS: Nicotine enhances the performance of archery athletes by increasing cognitive function and stimulating the sympathetic adrenergic system.

Association of body mass index with all-cause mortality in the elderly population of Taiwan: A prospective cohort study.

BACKGROUND AND AIMS: The nutritional status of the elderly is different from that of young people. Body composition changes as people age, for example, fat mass increases, muscle mass decreases, and body fat distribution is changed. We aimed to investigate the association of body mass index (BMI) with cause-specific mortality in the elderly population. METHODS AND RESULTS: The data of annual health examination for the older citizens (≥65 years old) from 2006 to 2011 in Taipei City Hospital were used. Information on baseline demographics, lifestyle behaviors, medical, and drug usage were collected by a self-administered questionnaire. Cause-specific mortality was ascertained from the National Registration of Death. Individuals were followed up until death or December 31, 2012, whichever was earlier. Univariable and multivariable Cox proportional hazard analyses were applied to investigate the association between BMI and all-cause mortality. Among 81,221 older people included in the analysis, 42,602 (52.45%) were men. The mean age was 73.85 ± 6.32 years. Among the 81,221 participants, 3398 (4.18%) were underweight, 36,476 (44.91%) were normal weight, 25,708 (31.65%) were overweight, and 15,639 (19.25%) were obese. Those in the BMI category 27 ≤ BMI<28 kg/m2 had the lowest all-cause mortality risk. The BMI of lowest cause-specific mortality was between 27 kg/m2 and 28 kg/m2 in infection mortality, between 28 kg/m2 and 29 kg/m2 in circulation mortality, between 29 kg/m2 and 30 kg/m2 in respiratory mortality, and between 31 kg/m2 and 32 kg/m2 in cancer mortality. CONCLUSIONS: The current study found a J-shaped relation between BMI and cause-specific mortality in the elderly population of Taiwan.

Prospective associations of physical fitness and cognitive performance among inpatients with Schizophrenia.

There is a paucity of longitudinal research investigating fitness and cognitive performance in people with schizophrenia. This study examined the prospective associations of physical fitness and cognitive performance among inpatients with schizophrenia. A prospective cohort study over two years was undertaken in 190 inpatients with schizophrenia. Four domains of physical fitness (body composition, muscle endurance, flexibility, and cardiovascular fitness) were measured at baseline in addition to the cognitive domains of attention, hand dexterity and working memory. At baseline, compared to general population normative data, more than one third of the sample had poor cardiovascular fitness, and over half were overweight/obese, had poor muscular fitness and poor flexibility. In the schizophrenia sample, better cardiovascular fitness at baseline was significantly associated with better attention, dexterity, and memory. However, the relationships dissipated after adjusting for baseline cognitive scores. In the final models, aside from baseline cognitive scores, only illness duration was significantly associated with dexterity, and smoking status and duration of hospitilization were associated with working memory. Our data suggest that in a cohort of people with established schizophrenia who already had evidence of cognitive dysfunction, better physical fitness was not associated with improved cognitive performance over two years.

Associations between walking parameters and subsequent sleep difficulty in older adults: A 2-year follow-up study.

PURPOSE: This 2-year follow-up study aimed to examine the associations between total volume, frequency, duration, and speed of walking with subsequent sleep difficulty in older adults. METHODS: A total of 800 older adults aged 65 years and over participated in the first survey in 2012 and 511 of them were followed 2 years later. The 5-item Athens Insomnia Scale (AIS-5) was used to measure sleep difficulty. Frequency, duration, and speed of outdoor walking were self-reported. Walking speed was assigned a metabolic equivalent value (MET) from 2.5 to 4.5. Total walking volume in MET-h/week was calculated as frequency × duration × speed. Negative binomial regressions were performed to examine the associations between volume and components of walking with subsequent sleep difficulty with covariates of age, sex, education, marital status, living arrangement, smoking, alcohol consumption, mental health, Charlson Index, exercise (excluding walking), and sleep difficulty at baseline. RESULTS: Participants with low walking volume had a higher level of sleep difficulty 2 years later compared with those with high walking volume (incident rate ratios = 1.61, p = 0.004). When speed, frequency, and duration of walking were simultaneously entered into 1 model, only walking speed was significantly associated with subsequent sleep difficulty (after the model was adjusted for covariates and baseline sleep difficulty). Sensitivity analyses showed that walking duration emerged as a significant predictor among 3 walking parameters, with 2-year changes of sleep scores as dependent variable. CONCLUSION: Total amount of walking (especially faster walking and lasting for more than 20 min) is associated with less subsequent sleep difficulty after 2 years among older adults.

Physical activity, smoking, and the incidence of clinically diagnosed insomnia.

OBJECTIVE: This study was designed to examine the independent and combined associations of physical activity and smoking on the incidence of doctor-diagnosed insomnia using a nationally representative sample over seven years, taking into account other relevant covariates. METHODS: Participants aged 18 years or older in the 2005 Taiwan National Health Interview Survey (NHIS) with links to National Health Insurance (NHI) claim data between 2005 and 2012 and without diagnosed insomnia before 2005, were selected into this study (n = 12,728). Participants were classified as having insomnia with International Classification of Diseases, Ninth Revision (ICD-9) CM codes 307.41, 307.42, or 780.52. Self-reported smoking status and frequency, duration, and types of leisure-time and non-leisure-time physical activities were collected. Metabolic equivalent (MET) intensity levels for each activity were assigned, and weekly energy expenditure of each activity was calculated and summed. RESULTS: Inactive participants had a higher risk of incident insomnia [hazard ratio (HR) = 1.22, 95% confidence interval (CI) = 1.06-1.42, p = 0.007] than the active group, and ever-smokers were more likely to have incident insomnia than never smokers (HR = 1.45, 95% CI = 1.20-1.76, p < 0.001). Compared with the nonsmoker/active group, the ever-smoker/inactive group had a higher risk of incident insomnia (HR = 1.78, 95% CI = 1.41-2.25, p < 0.001). Sensitivity analyses excluding individuals diagnosed with other sleep disorders or mental disorders yielded similar results, with the ever-smoker/inactive group having the highest risk of insomnia. CONCLUSIONS: Inactive adults and smokers are at higher risk for incident insomnia, highlighting the importance of a healthy lifestyle and pointing to strategies such as encouraging smoking cessation and physical activity to avoid insomnia among adults.

Associations of exercise, sedentary time and insomnia with metabolic syndrome in Taiwanese older adults: A 1-year follow-up study.

BACKGROUND: Understanding the risk factors of metabolic syndrome (MetS) is important to public health, since individuals with MetS have an increased risk of health problems. This study examined the associations of exercise, sedentary time and insomnia with incident MetS among older adults 1 year later. METHOD: A total of 1,359 older adults receiving hospital health examinations in 2012 were studied, and 779 subjects had a follow-up after 1 year. The components of MetS (waist, blood pressure, high-density lipoprotein cholesterol, fasting glucose and triglyceride) were defined by the Program's Adult Treatment Panel III report. Exercise, sedentary time and insomnia data were obtained through self-report questionnaires. Physical fitness (body fatness, balance and hand grip strength) was measured. Two logistic regressions were computed to examine the associations of exercise/physical fitness, sedentary time and insomnia at baseline with incident MetS 1 year later. The first regression included age, sex, smoking and alcohol as covariates. The second regression was further adjusted with the components of MetS. RESULTS: Sex, exercise/balance, sedentary time and insomnia were significant predictors of MetS. The risk of MetS incidence was 3.36 (95% CI 1.96-5.77) for women, 1.92 (95% CI 1.01-3.63) for those who did not exercise, 2.52 (95% CI 1.37-4.63) for those who sat more than 5 h/day, and 2.17 (95% CI 1.13-4.15) for those with insomnia. Poor balance was significantly associated with greater risk of MetS (AOR = 1.07, 95% CI 1.02-1.12). Sex, sedentary time, insomnia and balance remained significant after adjusting with the components of MetS. CONCLUSIONS: Cultivating exercise habits, reducing sedentary time and improving sleep quality may be important strategies for MetS prevention among older adults.

RAD001-mediated STAT3 upregulation and megakaryocytic differentiation.

RAD001 is currently used as an immunosuppressant and anticancer drug. Megakaryocyte (MK) differentiation includes development from pluripotent stem cells to proliferation and differentiation toward MK formation and platelet maturation. Our preliminary assay showed that RAD001 might stimulate MK differentiation; however, the exact regulatory mechanisms needed to be elucidated. By the ex vivo assay, RAD001 induced MK differentiation in human haematopoietic stem cells, with both the stimulation of CFU-GM colony formation and CD61 surface marker expression. Then, BALB/c mice were orally administrated with or without agrylin and/or RAD001 for 15 days. The platelet count and bone marrow CFU-MK colony formation were eliminated by agrylin, but unchanged in RAD001 and RAD001 plus agrylin mice. An ex vivo assay of bone marrow-derived stem cells demonstrated that RAD001 increased the number of CFU-MK colonies. The MK count in bone section indicated the decreased effect by agrylin and then recovered by RAD001. The level of plasma thrombopoietin was also enhanced in RAD001-treated mice. The effect of RAD001 on human leukaemic K562 and HEL cells showed the growth inhibition and MK differentiation activities; including morphological observation, CD41 and CD61 expression, and platelet factor 4 secretion. In RAD001-treated HEL cells, p-STAT3 expression, STAT3 translocation, and STAT3-DNA binding activity were up-regulated. Furthermore, STAT3 siRNA decreased the p-STAT3 and CD61 expression, as well as the CD61 fluorescence intensity, indicating that STAT3 may be critical in RAD001-mediated MK differentiation. Conclusion, the present study demonstrated that RAD001 might have the capacity to induce MK differentiation through the up-regulation of STAT3 signalling.

Relationships of leisure-time and non-leisure-time physical activity with depressive symptoms: a population-based study of Taiwanese older adults.

BACKGROUND: Limited research has explored the relationship between non-leisure-time physical activity (NLTPA), including domestic and work-related physical activities, with depressive symptoms. This study was designed to elucidate independent associations between leisure-time physical activity (LTPA), NLTPA, and specific parameters of physical activity (frequency, duration and intensity) with depressive symptoms in older adults. METHODS: A total of 2,727 persons aged ≥ 65 years participating in the 2005 Taiwan National Health Interview Survey were studied. Depressive symptoms were measured by the Center for Epidemiological Studies Depression Scale. Information regarding energy parameters for each type of LTPA and NLTPA during the past 2-week period was analyzed. After adjusting for socio-demographic variables, lifestyle behaviors and health status, multivariate logistic regression models were used to compute adjusted odds ratios (AOR) for LTPA and NLTPA for predicting depressive symptoms. RESULTS: LTPA but not NLTPA was significantly associated with depressive symptoms. Compared with participants expending 2000+ kcal/week through LTPA, the risk of experiencing depressive symptoms was significantly higher for those expending 1-999 kcal/week (AOR = 2.06, 95% CI: 1.25-3.39), and those who expending 0 kcal/week (AOR = 3.72, 95%CI: 2.28-6.06). Among the three parameters of LTPA (intensity, duration and frequency) examined, only intensity was independently associated with depressive symptoms. CONCLUSIONS: These findings imply that exercise recommendations for older adults should emphasize the importance of higher intensity activity, rather than frequency or duration, for improved mental well-being. However, well-designed prospective cohort studies or intervention trials are needed to confirm these findings.

Electrochemical release of hepatocyte-on-hydrogel microstructures from ITO substrates.

This paper describes a novel platform that utilizes micropatterning and electrochemistry to release cells-on-hydrogel microstructures from conductive indium tin oxide (ITO) substrates. In this approach, UV photopolymerization was employed to micropattern heparin-based hydrogels onto glass substrates containing ITO electrodes. ITO/glass substrates were first functionalized with acrylated silane to promote attachment of hydrogel structures. The surfaces containing hydrogel micropatterns were further functionalized with poly(ethylene glycol) thiol, rendering the regions around the hydrogel structures non-fouling to proteins and cells. After incubating surfaces with collagen (I), primary rat hepatocytes were shown to selectively attach on top of the hydrogel and not on surrounding glass/ITO regions. Electrical activation of specific ITO electrodes (-1.8 V vs. Ag/AgCl reference) was then used to release cells-on-hydrogel microstructures from the substrate. Immunostaining and reverse transcription polymerase chain reaction analysis of albumin, an important indicator of hepatic function, showed that the hepatocyte-on-hydrogel microstructures released from the surface maintained their function at levels similar to hepatocytes remaining on the culture substrate. In the future, switchable conductive substrates described here may be to collect cell samples at different time points and may also be used for harvesting cell-carrying vehicles for transplantation studies.

Characterization and Quantification of Nanoparticle-Antibody Conjugates on Cells Using C(60) ToF SIMS in the Event-By-Event Bombardment/Detection Mode.

Cluster C(60) ToF-SIMS (time-of-flight secondary ion mass spectrometry) operated in the event-by-event bombardment-detection method has been applied to: a) quantify the binding density of Au nanoparticles (AuNPs)-antiCD4 conjugates on the cell surface; b) identify the binding sites between AuNPs and antibody. Briefly, our method consists of recording the secondary ions, SIs, individually emitted from a single C(60) (1,2+) impact. From the cumulative mass spectral data we selected events where a specific SI was detected. The selected records revealed the SIs co-ejected from the nanovolume impacted by an individual C(60) with an emission area of ~ 10nm in diameter as an emission depth of 5-10 nm. The fractional coverage is obtained as the ratio of the effective number of projectile impacts on a specified sampling area (N(e)) to the total number of impacts (N(0)). In the negative ion mass spectrum, the palmitate (C(16)H(31)O(2) (-)) and oletate (C(18)H(33)O(2) (-)) fatty acid ions present signals from lipid membrane of the cells. The signals at m/z 197 (Au(-)) and 223 (AuCN(-)) originate from the AuNPs labeled antibodies (antiCD4) bound to the cell surface antigens. The characteristic amino acid ions validate the presence of antiCD4. A coincidence mass spectrum extracted with ion at m/z 223 (AuCN(-)) reveals the presence of cysteine at m/z 120, documenting the closeness of cysteine and the AuNP. Their proximity suggests that the binding site for AuNP on the antibody is the sulfur-terminal cysteine. The fractional coverage of membrane lipid was determined to be ~23% of the cell surfaces while the AuNPs was found to be ~21%. The novel method can be implemented on smaller size NPs, it should thus be applicable for studies on size dependent binding of NP-antibody conjugates.

The use of glass substrates with bi-functional silanes for designing micropatterned cell-secreted cytokine immunoassays.

It is often desirable to sequester cells in specific locations on the surface and to integrate sensing elements next to the cells. In the present study, surfaces were fabricated so as to position cytokine sensing domains inside non-fouling poly(ethylene glycol) (PEG) hydrogel microwells. Our aim was to increase sensitivity of micropatterned cytokine immunoassays through covalent attachment of biorecognition molecules. To achieve this, glass substrates were functionalized with a binary mixture of acrylate- and thiol-terminated methoxysilanes. During subsequent hydrogel photopatterning steps, acrylate moieties served to anchor hydrogel microwells to glass substrates. Importantly, glass attachment sites within the microwells contained thiol groups that could be activated with a hetero-bifunctional cross-linker for covalent immobilization of proteins. After incubation with fluorescently-labeled avidin, microwells fabricated on a mixed acryl/thiol silane layer emitted ∼ 6 times more fluorescence compared to microwells fabricated on an acryl silane alone. This result highlighted the advantages of covalent attachment of avidin inside the microwells. To create cytokine immunoassays, micropatterned surfaces were incubated with biotinylated IFN-γ or TNF-α antibodies (Abs). Micropatterned immunoassays prepared in this manner were sensitive down to 1 ng/ml or 60 pM IFN-γ. To further prove utility of this biointerface design, macrophages were seeded into 30 µm diameter microwells fabricated on either bi-functional (acryl/thiol) or mono-functional silane layers. Both types of microwells were coated with avidin and biotin-anti-TNF-α prior to cell seeding. Short mitogenic activation followed by immunostaining for TNF-α revealed that microwells created on bi-functional silane layer had 3 times higher signal due to macrophage-secreted TNF-α compared to microwells fabricated on mono-functional silane. The rational design of cytokine-sensing surfaces described here, will be leveraged in the future for rapid detection of multiple cytokines secreted by individual immune cells.