Unexpected roles for AMPK in the suppression of autophagy and the reactivation of MTORC1 signaling during prolonged amino acid deprivation.

AMPK promotes catabolic and suppresses anabolic cell metabolism to promote cell survival during energetic stress, in part by inhibiting MTORC1, an anabolic kinase requiring sufficient levels of amino acids. We found that cells lacking AMPK displayed increased apoptotic cell death during nutrient stress caused by prolonged amino acid deprivation. We presumed that impaired macroautophagy/autophagy explained this phenotype, as a prevailing view posits that AMPK initiates autophagy (often a pro-survival response) through phosphorylation of ULK1. Unexpectedly, however, autophagy remained unimpaired in cells lacking AMPK, as monitored by several autophagic readouts in several cell lines. More surprisingly, the absence of AMPK increased ULK1 signaling and MAP1LC3B/LC3B lipidation during amino acid deprivation while AMPK-mediated phosphorylation of ULK1 S555 (a site proposed to initiate autophagy) decreased upon amino acid withdrawal or pharmacological MTORC1 inhibition. In addition, activation of AMPK with compound 991, glucose deprivation, or AICAR blunted autophagy induced by amino acid withdrawal. These results demonstrate that AMPK activation and glucose deprivation suppress autophagy. As AMPK controlled autophagy in an unexpected direction, we examined how AMPK controls MTORC1 signaling. Paradoxically, we observed impaired reactivation of MTORC1 in cells lacking AMPK upon prolonged amino acid deprivation. Together these results oppose established views that AMPK promotes autophagy and inhibits MTORC1 universally. Moreover, they reveal unexpected roles for AMPK in the suppression of autophagy and the support of MTORC1 signaling in the context of prolonged amino acid deprivation. These findings prompt a reevaluation of how AMPK and its control of autophagy and MTORC1 affect health and disease.

Unexpected roles for AMPK in the suppression of autophagy and the reactivation of mTORC1 signaling during prolonged amino acid deprivation.

AMPK promotes catabolic and suppresses anabolic cell metabolism to promote cell survival during energetic stress, in part by inhibiting mTORC1, an anabolic kinase requiring sufficient levels of amino acids. We found that cells lacking AMPK displayed increased apoptotic cell death during nutrient stress caused by prolonged amino acid deprivation. We presumed that impaired autophagy explained this phenotype, as a prevailing view posits that AMPK initiates autophagy (often a pro-survival response) through phosphorylation of ULK1. Unexpectedly, however, autophagy remained unimpaired in cells lacking AMPK, as monitored by several autophagic readouts in several cell lines. More surprisingly, the absence of AMPK increased ULK1 signaling and LC3b lipidation during amino acid deprivation while AMPK-mediated phosphorylation of ULK1 S555 (a site proposed to initiate autophagy) decreased upon amino acid withdrawal or pharmacological mTORC1 inhibition. In addition, activation of AMPK with compound 991, glucose deprivation, or AICAR blunted autophagy induced by amino acid withdrawal. These results demonstrate that AMPK activation and glucose deprivation suppress autophagy. As AMPK controlled autophagy in an unexpected direction, we examined how AMPK controls mTORC1 signaling. Paradoxically, we observed impaired reactivation of mTORC1 in cells lacking AMPK upon prolonged amino acid deprivation. Together these results oppose established views that AMPK promotes autophagy and inhibits mTORC1 universally. Moreover, they reveal unexpected roles for AMPK in the suppression of autophagy and the support of mTORC1 signaling in the context of prolonged amino acid deprivation. These findings prompt a reevaluation of how AMPK and its control of autophagy and mTORC1 impact health and disease.

Trends and characteristics of Tai Chi and Qi Gong use among U.S. adults: Results from the 2007-2017 National Health Interview Survey.

OBJECTIVE: To provide updated information about the prevalence, patterns, and predicting factors of Tai Chi and Qigong (TCQ) use among U.S. adults to better inform the future directions of TCQ application and research. METHODS: Using 2007, 2012, and 2017 National Health Interview Survey, we examined the trends and characteristics of TCQ use by descriptive analysis, Wald F chi-square test, and multivariable logistic regression models among U.S. adults (n = 85,360), adjusting for the complex sampling design. RESULTS: The prevalence use of TCQ among U.S. adults use was 1.17% in 2007, 1.27% in 2012, and 1.70% in 2017, which presents a 64% increase from 2007 to 2017 (p < 0.0001). Correlates of TCQ use are older adults (≥ 65 years old), Asians, having higher education levels, having lower income, and being more physically active (p < 0.001). The greater prevalence of TCQ use in 2017 than in 2012 occurred in some vulnerable demographic subgroups, including older adults, people with income less than $35,000/year, and those who were physically inactive. Those with delayed access to the conventional medical care system (e.g., had difficulty getting through on phone; couldn't get an appointment soon enough; had to wait too long to see doctor;)were also more likely to use TCQ (p < 0.001). CONCLUSIONS: The use of TCQ has significantly increased among U.S. adults from 2007 to 2017. Given that the greatest increases in use of TCQ were among older adults, females, low-income individuals, and people who were physically inactive, TCQ may serve as age-appropriate, cost-effective, mind-body exercises for these groups of populations to help ameliorate health disparities.

Prevalence, patterns, and predictors of meditation use among U.S. children: Results from the National Health Interview Survey.

OBJECTIVES: The purpose of the study is to examine the characteristics of various types of meditation use (i.e., mantra, mindful, and spiritual meditation) among U.S. children. METHODS: Using 2017 National Health Interview Survey, we examined the prevalence, patterns, and potential predictors of meditation use among U.S. children aged 4 to 17 years. Descriptive statistics, Wald F chi-square test, and multivariable logistic regression were used for data analysis (n = 6925). RESULTS: Overall meditation use has increased substantially from 1.6% in 2012 to 7.4% in 2017 among children in the US. Children with chronic medical conditions were more likely to use mindful meditation (Adjusted Odds Ratio (AOR) = 1.9-3.6, 95% CI [1.0-7.4]). Regularly taking prescription medication had an inverse relation with mantra meditation use (AOR = 0.4, 95% CI [0.2-0.9]). Children with delayed medical care due to access difficulties were more likely to use spiritual meditation, compared to those who did not (AOR = 1.7, 95% CI [1.1-2.6]). CONCLUSIONS: Meditation use has rapidly increased among U.S. children within the past few years. Future studies should explore the underlying reasons for this increase and its potential benefits for pediatric meditators.

Trends in Yoga, Tai Chi, and Qigong Use Among US Adults, 2002-2017.

OBJECTIVES: To examine the characteristics and temporal trends of yoga, tai chi, and qigong (YTQ) use among US adults. METHODS: Using the 2002, 2007, 2012, and 2017 National Health Interview Surveys, we examined the prevalence, patterns, and predicting factors of YTQ use by Taylor series linear regression, the Wald F χ2 test, and multivariable logistic regression models (n = 116 404). RESULTS: YTQ use increased from 5.8% in 2002 to 14.5% in 2017 (P ≤ .001). Only 6.6% of YTQ users were referred by their medical doctors, and approximately one third disclosed their use of YTQ to medical professionals. Reasons for using YTQ included (1) YTQ was beneficial, (2) YTQ focused on the whole person, and (3) YTQ was natural. Acute and chronic pain, arthritis, and depression were the top 3 medical conditions for which people used YTQ the most. CONCLUSIONS: YTQ use is increasing substantially, mainly because of its natural and holistic healing approach toward health and chronic diseases. Future studies aiming to explore how to best integrate YTQ into the current health care system are warranted.

Association between psychological distress and elevated use of electronic devices among U.S. adolescents: Results from the youth risk behavior surveillance 2009-2017.

OBJECTIVE: The purpose of this study was to provide updated information about the prevalence and temporal trends of elevated use of electronic devices (EUED) in leisure time (i.e., 3 h or more on an average school day) in nationally representative samples of U.S. adolescents in recent years and to determine whether there is a significant association between EUED and psychological distress. METHODS: We used the national Youth Risk Behavior Survey (YRBS) data from 2009, 2011, 2013, 2015, and 2017 (N = 75,807). Propensity score matching was used to reduce selection bias due to potential confounding factors with EUED. Ordinal logistic regression analyses were performed for the matched samples to predict the association between EUED and psychological distress. RESULTS: The prevalence of EUED in U.S. youth has substantially increased from 24.9% in 2009 to 43.1% in 2017 (p < .001). Boys had higher rates of EUED than girls only in 2009 and 2011 but not in 2013, 2015, and 2017. A significant association between EUED and psychological distress was identified throughout all the five survey years. The odds of having a higher level of psychological distress increased approximately 1.5 times among youth with EUED than those without. CONCLUSIONS: The prevalence of U.S. youth with psychological distress and EUED has increased simultaneously in the past several years. Future longitudinal studies are warranted to examine causal and/or reciprocal relationship between the two.

Complementary and alternative medicine use among children with mental health issues: results from the National Health Interview Survey.

BACKGROUND: Mental health issues in children have become a serious public health concern in the U.S. within the past few decades. Emerging evidence suggests that Complementary and Alternative Medicine (CAM) can be beneficial for various mental health issues. However, little is known about the prevalence, reasons, and associated factors of CAM use among this population in the U.S. The purpose of this study is to examine the characteristics of CAM use among U.S. children with mental health issues. METHODS: Utilizing the 2012 National Health Interview Survey data, we used descriptive analysis, Wald F-statistics, and multivariable survey logistic regression models to examine the prevalence, patterns, and associated factors of CAM use in children aged 4-17 (n = 10,233) adjusting for the complex sampling design. RESULTS: CAM use is more popular among children with mental health issues compared with those without (19.2% vs. 10.1%, p < 0.001). Herbal remedies (9.1%), mind-body therapies (5.5%), and chiropractic care (5.3%) were the most frequently used modalities. Primary reasons for children to use CAM are because they are helpful (69.2%), natural (55.9%), and holistic (44.7%). The majority of CAM users perceived CAM therapies are helpful. Predictors of CAM use are children who are female, whose parents had a higher educational level and socioeconomic status, and who had at least one co-morbid medical condition. Only 18.4% of CAM usage was recommended by medical doctors. CONCLUSIONS: Approximately 10 million parents of children with mental health issues reported the use of CAM therapies, mainly because of their desire for a more natural and holistic healthcare approach. Given that the majority of CAM users perceived CAM therapies as helpful, future studies should investigate the unique contributions of CAM in pediatric psychiatric care. Because a low percentage of CAM use was recommended by medical doctors, educational interventions designed to equip medical professionals with CAM knowledge and experience will be conducive to improving effective patient-physician communication in clinical settings. Since CAM use is reported as more prevalent by parents' of children with higher education and family income, effective strategies designed to reduce disparities in accessing promising CAM therapies are warranted.

Body Weight and Bullying Victimization among US Adolescents.

OBJECTIVE: We examined the association between body weight status at all levels (including underweight, normal weight, overweight, and obesity) and bullying victimization among US ado- lescents using a nationally representative data. METHODS: We used logistic regression to exam- ine the association between bullying victimization and body weight status by sex with the data from the 2013 Youth Risk Behavior Survey (YRBS) (N = 11,825), controlling for demographics, selected behavioral confounders, and complex survey design. RESULTS: We found a statistically significant U-shaped association between body weight and bullying victimization among male (p = .001) but not female students (p = .838). For girls, the prevalence of being bullied slightly increased from underweight (33.58%) to normal weight (34.36%) to obesity (36.18%) but such increases failed to reach statistical significance. For boys, being bullied was significantly associ- ated with younger age, being white, feeling hopeless, having suicidal ideation, and excessive video-game playing. CONCLUSIONS: A U-shaped association between body weight and bullying victimization appears to exist in boys but not girls, partly because of the body weight stigma and sex stereotypes among US adolescents. Future studies should investigate the risk factors associated with sex-specific bullying to develop effective anti-bullying programs for youth.

Optical Verification of Microbubble Response to Acoustic Radiation Force in Large Vessels With In Vivo Results.

OBJECTIVE: The objective of this study was to optically verify the dynamic behaviors of adherent microbubbles in large blood vessel environments in response to a new ultrasound technique using modulated acoustic radiation force. MATERIALS AND METHODS: Polydimethylsiloxane (PDMS) flow channels coated with streptavidin were used in targeted groups to mimic large blood vessels. The custom-modulated acoustic radiation force beam sequence was programmed on a Verasonics research scanner. In vitro experiments were performed by injecting a biotinylated lipid-perfluorobutane microbubble dispersion through flow channels. The dynamic response of adherent microbubbles was detected acoustically and simultaneously visualized using a video camera connected to a microscope. In vivo verification was performed in a large abdominal blood vessel of a murine model for inflammation with injection of biotinylated microbubbles conjugated with P-selectin antibody. RESULTS: Aggregates of adherent microbubbles were observed optically under the influence of acoustic radiation force. Large microbubble aggregates were observed solely in control groups without targeted adhesion. Additionally, the dispersion of microbubble aggregates were demonstrated to lead to a transient acoustic signal enhancement in control groups (a new phenomenon we refer to as "control peak"). In agreement with in vitro results, the control peak phenomenon was observed in vivo in a murine model. CONCLUSIONS: This study provides the first optical observation of microbubble-binding dynamics in large blood vessel environments with application of a modulated acoustic radiation force beam sequence. With targeted adhesion, secondary radiation forces were unable to produce large aggregates of adherent microbubbles. Additionally, the new phenomenon called control peak was observed both in vitro and in vivo in a murine model for the first time. The findings in this study provide us with a better understanding of microbubble behaviors in large blood vessel environments with application of acoustic radiation force and could potentially guide future beam sequence designs or signal processing routines for enhanced ultrasound molecular imaging.