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Risk factors for motor coordination problems in preschool‐age children
Abstract
Background
Motor coordination problems (MCP) in children can sometimes be diagnosed as developmental coordination disorder. Early intervention for developmental coordination disorder is necessary because it often continues into adolescence, causing mental and physical complications. Few studies have investigated the prevalence of childhood MCP in the Japanese population, examining the risk factors for MCP. We therefore investigated the prenatal factors associated with MCP in preschool‐age children.
Methods
This study was based on a prospective cohort study, the Hokkaido Study on Environment and Children’s Health. Mothers of 4,851 children who reached the age of 5 years within the study‐period received questionnaires, including the Japanese version of the Developmental Coordination Disorder Questionnaire (DCDQ‐J). We examined the risk factors associated with MCP using logistic regression analysis.
Results
Of 3,402 returned DCDQ‐J questionnaires, 3,369 were answered completely. From the 3,369 children, we categorized having MCP by using two cut‐off scores: that of the DCDQ’07 and the cut‐off at the 5th percentile of a total DCDQ‐J score. Comparing children with and without MCP, we found significant differences in the education level of the mothers, annual household income during pregnancy, maternal alcohol consumption and smoking during pregnancy, and sex and age of the children at the time of completing the DCDQ‐J by both categorizations. Adjusted logistic regression analysis revealed that maternal smoking during the first trimester of pregnancy and male sex were significantly associated with MCP.
Conclusions
Our results suggest that maternal smoking during pregnancy is the main factor associated with MCP in preschool‐age children.
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P KZN NAFLD X BCAA
A branched‐chain amino acid‐based metabolic score can predict liver fat in children and adolescents with severe obesity
Abstract
Background
Eighty percent of adolescents with severe obesity suffer from non‐alcoholic fatty liver disease (NAFLD). Non‐invasive prediction models have been tested in adults, however, they performed poorly in paediatric populations.
Objective
This study aimed to investigate novel biomarkers for NAFLD and to develop a score that predicts liver fat in youth with severe obesity.
Methods
From a population with a BMI >97th percentile aged 9‐19 years (n = 68), clinically thoroughly characterized including MRI‐derived proton density fat fraction (MRI‐PDFF), amino acids and acylcarnitines were measured by HPLC‐MS.
Results
In children with NAFLD, higher levels of plasma branched‐chain amino acids (BCAA) were determined. BCAAs correlated with MRI‐PDFF (R = 0.46, p < .01). We identified a linear regression model adjusted for age, sex and pubertal stage consisting of BCAAs, ALT, GGT, ferritin and insulin that predicted MRI‐PDFF (R = 0.75, p < .01). ROC analysis of this model revealed AUCs of 0.85, 0.85 and 0.92 for the detection of any, moderate and severe steatosis, respectively, thus markedly outperforming previously published scores.
Conclusion
BCAAs could be an important link between obesity and other metabolic pathways. A BCAA‐based metabolic score can predict steatosis grade in high‐risk children and adolescents and may provide a feasible alternative to sophisticated methods like MRI or biopsy in the future.
1 INTRODUCTION
Despite major public health efforts to avoid overnutrition, the global prevalence of obesity is still rising, and concomitantly, the prevalence of non‐alcoholic fatty liver disease (NAFLD).1 NAFLD is an important predictor for mortality2 and is known to increase the risk of type 2 diabetes, cardiovascular disease and dyslipidemia,3, 4 already in youth with obesity.3, 5 NAFLD is often the first comorbidity that arises in obesity6 and the degree of liver fat content relates to the grade of metabolic disease,7-9 underlining the importance of steatosis as an early indication of metabolic disease. However, the underlying pathomechanisms are poorly understood.9
The need for characterization of a high‐risk group for NAFLD and targeted approaches early in life was formally acknowledged by the Committee on prevention of obesity in children and youth of the U.S. Institute of Medicine.10 Reliable quantitative determination of liver fat content, however, is based on either biopsy or sophisticated imaging techniques11 only available in specialized centres. Thus, there is a vital need for reliable but simple biomarkers for quantification of liver fat content. To this objective, biochemical markers and routine measures have been evaluated. GGT and ALT, known measures of liver disease, have been proposed as independent predictors of NAFLD.12 However, Wong et al. found that ALT levels show a high variability on repeated testing and do not reliably diagnose NAFLD nor correlate with histologic grading.13 Therefore, metabolic risk factors were proposed as the basis of NAFLD evaluation, but most studies are limited by evaluating NAFLD solely as a dichotomous parameter.14-17 Liver fat content seems to directly relate to the degree of metabolic disease and should therefore be quantitatively determined.18, 19
Metabolomics approaches showed that amino acid patterns are more strongly associated with metabolic health than traditional laboratory and also lipid markers.20 Big cohorts identified circulating branched chain amino acids (BCAAs) to be chronically elevated in individuals with obesity. Compelling evidence derived from rodent studies highlights their causal connection to the risk of T2D and insulin resistance and cardiovascular disease.21-23 Hence, elevated BCAAs are characteristic for deteriorated metabolic health20, 22, 24, 25 already early in life16, 18 and predict future disease risk.16, 22, 26 BCAAs have been shown to promote intrahepatic fat accumulation in an animal model27 and are elevated in human individuals with NAFLD,14-19 suggesting a link between impaired amino acid metabolism and liver fat accumulation.17 The aetiology and pathophysiological pathways of increased BCAA levels in obesity is still unclear, but may involve chronic low grade inflammation by inducing pro‐inflammatory gene expression in adipose tissue,28, 29 thereby further deteriorating obesity effects on metabolic health, also in cardiovascular24, 25 and liver disease.27
Substantial evidence that links BCAA dysmetabolism to a metabolically unhealthy phenotype with obesity including steatosis, hepatic injury or inflammation14-19, 27, 30 has been published. Therefore, defining a BCAA‐related metabolic signature that indicates the liver fat content could not only help to identify and monitor patients with NAFLD and increased cardiometabolic risk,5, 21, 23-26 but also to elucidate the underlying pathomechanisms.
Early interference in paediatric patients to prevent progression of NAFLD and other obesity‐related disorders is highly desirable.2, 10 Furthermore, the pathogenesis of NAFLD in children and adolescents is much less investigated and may significantly differ compared to adults.31 Therefore, studies in paediatric patients are strongly needed. The only existing study with an accurate quantification of liver fat content by MRI analyzing amino acid levels in children and adolescents investigated a majority of non‐Caucasian individuals.18 Plasma concentrations of BCAAs were shown to be associated with intra‐hepatic fat content independently of the degree of obesity and insulin resistance.18 Although these results may not directly be applicable to European cohorts,9, 32 they provide a strong indication for BCAAs to be investigated in Caucasian paediatric patients in relation to NAFLD. Same accounts for acylcarnitines, which are not only linked to fatty acid metabolism but some of the shorter forms also to BCAA metabolism. Interestingly, the latter have been shown to be linked to insulin resistance.15, 21, 26
To fill these gaps in research in the high‐risk group of youths with severe obesity and to further contribute to elucidation of the complex mechanisms leading to paediatric NAFLD, we investigated whether circulating amino acid levels are associated with liver fat content as measured by MRI in children and adolescents with severe obesity. Moreover, a plethora of amino acids, acylcarnitines and established clinical as well as experimental markers for liver function, metabolic state, and inflammation was considered for development of a simple and thus practicable score to predict liver fat content. The resulting score includes BCAAs, ALT, GGT, ferritin and insulin to predict liver fat content in paediatric patients with severe obesity with high accuracy.
2 METHODS
2.1 Patients
Patients attending the outpatient clinic for obesity and lipid‐metabolic disorders at the Department of Pediatrics and Adolescent Medicine at the Medical University of Vienna with a BMI above the 97th percentile (referred to as “severe obesity”33, 34 throughout this manuscript) were prospectively enrolled in this study. Eligible for this study were all patients between 9 to 19 years old. Patients were excluded if one or more of the following exclusion criteria were met: Chromosomal aberrations and syndromes associated with obesity (eg, Prader‐Willi‐Syndrome), treatment with drugs associated with elevated liver enzymes and if other causes for liver disease were present (eg, Wilson's disease, hepatitis infection). Of 94 eligible patients, 68 were included in the study. Twenty‐six patients were excluded, because of incompliance with study protocol. Subsequently, a second cohort of 32 paediatric patients was recruited for independent validation.
All study participants underwent physical examination including Tanner stage. Medical history, clinical and laboratory data was collected for all study participants. Anthropometric measures were taken by standardized methods by the same two nurses throughout the study. Body mass index (BMI, kg/m2) and the respective percentiles and SD scores were calculated according to Kromeyer‐Hauschild et al.35 Body fat in percent (body fat%) was determined by bioelectrical impedance analysis (BIA). Serum and plasma samples were taken in an overnight fasting state and, for non‐routine parameters, frozen at −80°C until analysis. Homeostasis model of insulin resistance (HOMA‐IR) was calculated according to Matthews et al.: fasting glucose (mmol/L) * fasting insulin (mU/L)/22.5.36
2.2 Liver fat content
Accumulation of liver fat was quantified by magnetic resonance imaging‐proton density fat fraction (MRI‐PDFF). MRI scan was performed at the Department of Biomedical Imaging and Image‐guided Therapy, Medical University of Vienna, on a 1.5 Tesla MR‐Scanner Siemens Magnetom Aera. Image data was evaluated using a PACS (picture archiving and communication system, IMPAX EE, Agfa Healthcare, Mortsel, Belgium) on a diagnostic grey‐scale monitor (Barco MDCG‐3120, Brussels, Belgium). For MRI‐PDFF calculation, one MR‐slice of in‐phase sequence and the corresponding slice of opposed‐phase sequence were used. The quality of MR‐images was evaluated by a senior radiologist (A.H.). In the case of severe motion artefacts, which reduce the diagnostic image quality, patients would have been excluded, which was never the case. MRI‐PDFF was calculated according to Sirlin et al.37 and was calculated and interpreted by the same senior radiologist (A.H.) in all patients. Steatosis was defined as a MRI‐PDFF of 5.1% or more. Mild steatosis (grade 1) was specified as a MRI‐PDFF below 14.1%, moderate steatosis (grade 2) below 28.0% and a MRI‐PDFF of 28.0% and above was defined as severe steatosis (grade 3).38, 39
2.3 Amino acids and acylcarnitines
Plasma amino acid and acylcarnitine concentrations were determined on a Waters Acquity UPLC‐coupled Xevo TQD mass spectrometer using non‐derivatized a semi‐quantitative kit for dried blood spots from Chromsystems (Gräfeling, Germany), which was modified by directly pipetting 1.3 μL plasma, sampled and stored as described above, into extraction buffer. For confirmation, amino acids were additionally quantified from fresh plasma of 30 of the patients using the EZ:faast kit from Phenomenex (Torrance, CA) on a Waters Q‐Micro HPLC‐coupled mass spectrometer with essentially same results (not shown). BCAA concentrations were calculated by addition of valine, leucine and isoleucine values.
2.4 Calculation of known scores
Enhanced liver fibrosis (ELF) test,40 fatty liver index (FLI),41 GSG index,14 hepatic steatosis index (HSI),42 visceral adiposity index (VAI)43 and triglycerides glucose (TyG) index44 were calculated exactly as described in the given references.
2.5 Statistics
In order to perform group‐wise comparisons, steatosis was categorized as described above. Ordinal scaled data was analyzed with the ANOVA. For normally distributed variables, correlation among parameters was assessed by Pearson correlation analyses. For skewed variables, Spearman correlation was calculated.
Analyzed parameters included: BMI z‐score, body fat, waist circumference, hip circumference, ferritin, uric acid, platelets, alkaline phosphatase, GGT, ALT, AST, bilirubin, triglycerides, total cholesterol, fasting glucose, insulin, HOMA‐IR, CRP, IL6, procalcitonin, TNFα, CK‐18, BCAAs, the amino acids alanine, aspartic acid, glutamic acid, glycine, proline, tyrosine, arginine, phenylalanine, ornithine, citrulline and acylcarnitines propionylcarnitine (C3), butyrylcarnitine (C4) and isovalerylcarnitine (C5), hexanoylcarnitine (C6), octanoylcarnitine (C8), decanoylcarnitine (C10), dodecanoylcarnitine (C12), tetradecanoylcarnitine (C14), hexadecanoylcarnitine (C16) and stearoylcarnitine (C18). Partial least squares regression was performed to identify the statistically most important variables: Variables with a variable importance in projection (VIP) >1 were selected for further analysis.45, 46 In the next step, variables were entered into a multiple linear regression analysis to assess independent association. In the linear regression model, each indicator was assessed as an independent variable and MRI‐PDFF as dependent variable. Covariates were selected from known predictors of childhood obesity.
The predictive value of our model was assessed by the area under the receiver operating characteristic curve (AUROC, c statistic). The score characteristics, sensitivity and specificity, were calculated. In order to estimate the clinical use of our model, positive predictive value (PPV) and negative predictive value (NPV) were calculated to determine the probability of the disease in the individual patient.
All analyses were conducted without stratification because we found no interaction attributable to sex or age. A two‐sided p‐value under .05 was considered statistically significant. All statistical analyses were performed using IBM SPSS Statistics for Windows, version 25 (IBM Corp., Armonk, New York).
2.6 Ethics
The study protocol was approved by the ethics committee of the Medical University of Vienna (No. 1638/2019) and conducted according to the Helsinki declaration guidelines. Written informed consent was obtained from all participants as well as their legal guardians prior to all study procedures.
3 RESULTS
Characteristics of the study population are shown in Table 1. Sixty‐eight patients with mean age of about 13 years completed MRI evaluation of the liver and were included in the study. All were of Caucasian ethnicity. Of the investigated parameters, HOMA‐indices, liver transaminases, GGT, total cholesterol, insulin, triglycerides, ferritin, PCT, TNFα and CK‐18 significantly correlated with liver fat content (p‐value ≤ .02 for all, Table S1).
No steatosis (n = 33) | Mild steatosis (n = 16) | Moderate steatosis (n = 18) | Severe steatosis (n = 12) | p‐value | ||
---|---|---|---|---|---|---|
Gender | (female/male) | 14/19 | 6/10 | 4/14 | 3/9 | n.s. |
Age | 13.00 (3.00) | 13.00 (3.00) | 13.00 (3.00) | 13.00 (2.00) | n.s. | |
BMI z‐score | 5.89 (9.95) | 4.79 (8.42) | 9.71 (13.87) | 7.77 (11.13) | n.s. | |
Waist circumference (cm) | 109.56 (23.05) | 107.14 (19.23) | 119.09 (29.57) | 120.44 (27.78) | n.s. | |
Hip circumference (cm) | 110.97 (14.95) | 107.27 (13.17) | 109.51 (11.99) | 114.35 (20.45) | n.s. | |
BIA (body fat%) | 40.29 (7.20) | 41.66 (6.32) | 38.88 (5.24) | 40.14 (6.86) | n.s. | |
HOMA‐IR | 2.96 (1.95, 4.43) | 5.26 (3.06, 8.44) | 5.34 (5.00, 6.49) | 6.84 (5.41, 9.82) | <.01 | |
HOMA‐β | 3.72 (2.37, 5.38) | 7.14 (3.85, 11.10) | 6.87 (5.84, 9.61) | 8.12 (6.80, 9.99) | <.01 | |
Fasting glucose (mg/dl) | 81.00 (9.43) | 82.38 (11.28) | 87.09 (12.07) | 83.35 (7.60) | n.s. | |
Insulin (μU/ml) | 14.16 (8.77) | 29.98 (20.83) | 25.86 (22.77) | 26.76 (17.8) | .02 | |
Ferritin (μg/l) | 44.11 (21.66) | 57.38 (36,24) | 60.78 (30,82) | 144.93 (149.71) | .01 | |
Platelet count (10̂9/L) | 277.47 (54.00) | 303.81 (66.00) | 315.06 (78.00) | 280.33 (49.40) | n.s. | |
AP (U/l) | 162.45 (85.47) | 177.31 (61.54) | 173.94 (80.83) | 188.25 (82.17) | n.s. | |
GGT (U/l) | 19.27 (11.37) | 56.67 (125.98) | 30.28 (25.66) | 42.58 (28.74) | <.01 | |
ALT (U/l) | 29.36 (9.89) | 46.75 (42.83) | 52.39 (32.27) | 116.08 (97.31) | <.01 | |
AST (U/l) | 26.33 (5.73) | 36.44 (17.65) | 36.33 (15.38) | 61.00 (37.38) | <.01 | |
Triglycerides (mg/dl) | 89.00 (71.00, 122.00) | 131.00 (104.00, 184.00) | 115.00 (89.00, 221.00) | 145.00 (98.00, 212.00) | <.01 | |
Total cholesterol (mg/dl) | 155.00 (141.00, 187.00) | 164.00 (160.00, 188.00) | 163.00 (153.00, 202.00) | 181.00 (158.00, 218.00) | n.s. | |
HDL‐C (mg/dl) | 45.00 (38.00, 48.00) | 42.00 (31.00, 50.00) | 43.00 (39.00, 46.00) | 39.00 (33.00, 43.00) | n.s. | |
Uric acid (mg/dl) | 5.25 (1.77) | 5.99 (1.78) | 4.31 (2.69) | 5.52 (2.77) | n.s. | |
ELF test | 8.60 (0.79) | 8.63 (0.58) | 8.90 (0.55) | 8.61 (0.72) | n.s. | |
CRP (mg/dl) | 0.72 (0.28, 1.24) | 0.70 (0.47, 0.97) | 0.33 (0.18, 1.27) | 0.85 (0.25, 3.33) | n.s. | |
IL‐6 (pg/ml) | 3.32 (1.50, 5.01) | 2.88 (1.50, 4.58) | 2.90 (1.50, 3.64) | 2.90 (2.21, 4.25) | n.s. | |
Procalcitonin (ng/ml) | 0.04 (0.03, 0.06) | 0.05 (0.03, 0.05) | 0.05 (0.04, 0.09) | 0.07 (0.04, 0.09) | n.s. | |
TNFα (pg/ml) | 1.05 (0.90, 1.25) | 1.25 (0.95, 1.60) | 1.00 (0.75, 1.50) | 1.55 (1.30, 1.65) | .03 | |
CK‐18 (U/l) | 92.48 (83.57, 134.53) | 101.10 (83.57, 204.63) | 107.87 (99.80, 148.40) | 212.33 (141.73, 385.79) | <.01 | |
BCAAs (μmol/l) | 461.62 (81.14) | 490.29 (108.74) | 491.40 (60.29) | 545.56 (80.15) | <.01 | |
C3 (μmol/l) | 0.48 (0.16) | 0.60 (0.28) | 0.72 (0.28) | 0.68 (0.20) | .01 | |
C4 (μmol/l) | 0.20 (0.08) | 0.24 (0.12) | 0.28 (0.12) | 0.36 (0.12) | <.01 | |
C5 (μmol/l) | 0.12 (0.04) | 0.16 (0.04) | 0.20 (0.16) | 0.20 (0.32) | n.s. |
- Note: Values are means and (SD) for normally distributed variables and median (25th, 75th percentile) for skewed variables. p‐values less than .05 was considered significant and were determined by ANOVA or Kruskal Wallis test, respectively.
- Abbreviations: AP, alkaline phosphatase; BMI, body mass index; BIA (body fat%), body fat in % determined by bioelectrical impedance analysis; ELF, enhanced liver fibrosis; HOMA‐IR, homeostatic model assessment of insulin resistance; HOMA‐β, homeostatic model assessment of liver insulin resistance.
To assess the metabolic profile of the patients, 10 amino acids and 10 acylcarnitines were determined and exploratively analyzed for associations. In particular BCAAs and related acylcarnitine concentrations appeared to be linked to fatty liver: The correlation of BCAAs with liver fat content (p‐value < .01, R = 0.46) also after adjustment for gender, age and pubertal stage is shown in Figure 1. Additionally, the ANOVA showed significant differences in BCAA levels between steatosis stages (p‐value .03). Also concentrations of acylcarnitines C3 and C4 significantly differed between the groups (Table 1), moreover, acylcarnitines C3, C4 and C5, byproducts of BCAA degradation, correlated with MRI‐PDFF (Table 2), essentially confirming the BCAA results. Moreover, BCAAs and C3, C4, C5 significantly correlated with ALT and CK‐18 as markers for advanced steatosis (Table 2). Also HOMA‐β and HOMA‐IR correlated with BCAAs, C3, C4 and C5 (Table 2).
MRI‐PDFF | ALT (U/l) | TNFα | CK‐18 | HOMA‐IR | ||||||
---|---|---|---|---|---|---|---|---|---|---|
R | Sig. | R | Sig. | R | Sig. | R | Sig. | R | Sig. | |
C3 | 0.43 | <0.01 | 0.40 | <0.01 | 0.24 | 0.09 | 0.26 | 0.04 | 0.31 | 0.02 |
C4 | 0.42 | <0.01 | 0.42 | <0.01 | 0.59 | <0.01 | 0.26 | 0.04 | 0.29 | 0.03 |
C5 | 0.25 | 0.04 | 0.40 | <0.01 | 0.23 | 0.11 | 0.45 | <0.01 | 0.30 | 0.02 |
BCAAs | 0.46 | <0.01 | 0.46 | <0.01 | 0.20 | 0.20 | 0.30 | 0.02 | 0.49 | <0.01 |
3.1 Linear regression model
Despite the strong and significant correlation of BCAAs and some acylcarnitines with liver fat content, their analytical value is limited when considered in isolation. Therefore, a linear regression model was built as detailed in the Material and Methods section. Parameters primarily taken into account included anthropometric measures, routine laboratory parameters (eg, liver enzymes), markers of inflammation (eg, TNFα, IL‐6, CRP) and markers of liver status (eg, uric acid, procalcitonin, ferritin) as well as amino acids and acylcarnitines. The model was adjusted for age, sex and pubertal stage. The final model to predict hepatic fat content (MRI‐PDFF) consisted of the parameters BCAAs, ALT, GGT and insulin and is defined as follows (p‐value < .01; R = 0.75, R2 = 0.57, Figure 2): Predicted MRI‐PDFF = BCAAs (μmol/l) * 0.03 + ALT (U/l) * 0.144 + GGT (U/l) * (−0.208) + Ferritin (μg/l) * 0.041 + Insulin (μU/ml) * 0.313‐14.04.
Accuracy of the model was assessed by the c‐statistic (AUROC). ROC curves are shown in Figure 3. AUC was 0.85 (95%CI 0.76‐0.95) for the diagnosis of any steatosis (MRI‐PDFF >5.1%) and 0.85 (95%CI 0.76‐0.95) for the diagnosis of at least moderate steatosis (MRI‐PDFF >14.1%). For severe steatosis (MRI‐PDFF>28%) the AUC was 0.92 (95%CI 0.84‐0.99).
3.2 Model evaluation
In the next step, we assessed how our model performed compared to previously published scores with c‐statistic. Notably, our model had a higher accuracy than previously proposed scores for the detection of steatosis in children with severe obesity (Figure 4).
The ability of our model to detect patients with at least mild steatosis (>5.1% MRI‐PDFF) was 91.7% (=sensitivity), while specificity to detect patients without the disease was 35%.
Among those who had positive tests for mild steatosis (predicted value >5.1%), the probability of having steatosis (=PPV) was 73.3%. Among those who had negative Test (<5.1%), the probability of being disease free (=NPV) was 75%.
For the detection of at least moderate steatosis, the sensitivity was 71.4%, specificity 85.7%, PPV 75% and NPV 83.3%.
We validated our model in an independent validation cohort of 32 patients (Table S2). Performance of the BCAA‐based model was evaluated by calculating the AUC (Table S3). AUC was 0.82 (95%CI 0.67‐0.97) for the diagnosis of any steatosis (MRI‐PDFF >5.1%) and 0.92 (95%CI 0.83‐1.00) for the diagnosis of at least moderate steatosis (MRI‐PDFF >14.1%). For severe steatosis (MRI‐PDFF>28%) the AUC was 0.90 (95%CI 0.75‐1.00). AUCs were highest for the BCAA‐based model, thus outperforming previously published scores and indices also in the validation cohort and confirming the results of the original cohort.
4 DISCUSSION
Here, we show that an incomplex model is able to accurately predict fatty liver. Since childhood obesity is a major health threat worldwide, as is concomitantly NAFLD, our score may be valuable to recognize high‐risk individuals early on to start targeted prevention and treatment strategies. Starting interventions as early as possible is crucial to prevent further progress of liver disease and the development of other comorbidities like type 2 diabetes and cardiovascular disease. Since steatosis is an early predictor of cardiometabolic disease4 but can be reliably determined only by biopsy or sophisticated imaging techniques, a simple tool for early recognition and risk stratification as well as for subsequent monitoring as presented here may be of high clinical value. Considering the impact of these disorders for children and adolescents, this notion applies particularly for paediatric patients. Amino acids can readily be quantified from plasma or from dried blood spot specimen, which enable easy sampling and shipping, by metabolic labs. This may open interesting options in particular for disease monitoring and to increase patients' compliance as compared to time‐consuming MRI.
Strikingly, the BCAA‐based metabolic score markedly outperformed proposed indices like HIS, FLI, VAI and TyG for prediction of liver fat content. Besides the inclusion of BCAAs, the better performance of the score presented here can be attributed to the fact that adult NAFLD is markedly different from paediatric NAFLD. ELF test, a relatively cost‐intensive test that combines four different biochemical markers, was also tested as a marker for NAFLD in children with obesity.40 However, ELF test performed poorly in our study since it showed no association with steatosis grade and an AUC value of 0.57 (not shown).
The clinical relevance of our score was evaluated with the PPV and NPV. Based on the high PPV and NPV for the detection of mild and especially moderate steatosis, we conclude that our model can differentiate between individuals who have steatosis and those who do not. The ability of our model to detect patients with the disease was 91.7%.
In agreement with our study, previous studies concluded that BCAA dysmetabolism characterizes pathogenesis of NAFLD18 and showed that biopsy‐proven liver damage displayed increased values of BCAAs.14 Indeed, in our prediction model BCAAs were one of the key factors for predicting hepatic fat accumulation. Thus, our results further support the potential diagnostic value of BCAAs in NAFLD.
Our data do not support a link of inflammation (as determined by TNFα, IL‐6, procalcitonin and CRP values) to BCAA concentrations, thus the mechanisms underlying increased BCAA levels in obesity remain unclear. Decreased expression of catabolic enzymes like branched chain keto acid dehydrogenase kinase may be a factor explaining chronically increased circulating BCAA levels.30, 47 As a consequence of enhanced BCAA levels, chronic activation of mTOR may be induced leading to increased oxidative stress (ROS) and suppressed autophagy48, 49 and thus may promote lipid accumulation and lipotoxic liver injury.27, 48 Therefore, the underlying pathways linking BCAA metabolism to metabolic disease could potentially be pharmacologically targeted to improve hepatic and overall insulin resistance as well as reduction of liver fat content, underlining the utmost importance of further investigations in this field.30
5 LIMITATIONS
One limitation of the current study is the relatively small sample size. Hence, external validation of our proposed score in bigger cohorts is needed. Since we only included youth with severe obesity from our tertiary care centre in Vienna, Austria, the utility of our score in children with normal weight and of non‐Caucasian ethnicity remains to be determined.
Strengths of this study include its prospective character providing a close correlation between blood sampling and liver MRI, which were all performed within a short time frame (8 weeks). Additionally, strict criteria of inclusion were followed: All patients were extensively tested and excluded from this study if autoimmune, infectious or drug‐induced liver disorder was suspected providing a well‐characterized homogenous cohort. Importantly, all tests were corrected for age, gender and pubertal stage.
6 CONCLUSIONS
Elevated circulating BCAAs could be an important link between obesity, NAFLD and other metabolic pathways involved in lipid and glucose metabolism. They may distinguish metabolically healthy from metabolically impaired youth with obesity. A simple BCAA‐based metabolic score predicted steatosis grade in the high‐risk group of children and adolescents with severe obesity and may provide a feasible complement or alternative to current diagnostic measures.
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GRATITUDE IS A PRACTICE
GT GON P T X JFS X GON PRNTS TCHRS X JB FMLY SCTY
What I’m looking for is not out there, it is in me.” ~Helen Keller
I used to think that life should be easy, and if it wasn’t easy, then I was doing it wrong.
I’m older and wiser now, and I’ve learned that if it is hard, that means I am probably doing something right.
I had a good childhood. I had a loving family, plenty of opportunity, and I excelled at whatever I put my mind to. But I was a high-anxiety kid, and a relentless perfectionist. As I grew older, that need to have everything flawless impeded my ability to be happy because I didn’t like myself very much.
When I got married, I felt like I had added a notch to my self-worth belt. As someone who didn’t have a whole lot of self-esteem or love for herself, when someone else loved me, it was just what I needed to feel validated, or so I thought.
But that wore off too.
Then, I had kids, which was amazing—I love being a mom. But there was still something missing. I was happy enough, but I didn’t feel alive. There was this little whisper the whole time that said you are not where you’re supposed to be.
I felt this urgency to figure out how to be happy, but at the same time, I didn’t. I was happy enough, and there was that guilt. I should be happy. I was so blessed with two beautiful children, a husband, a gorgeous home—you know, the American dream. I’m a terrible, selfish person if I’m not thankful for everything I’ve been blessed with.
And life was comfortable. It wasn’t what I had dreamed of, or as beautiful as I had thought it would be, but everything was “fine.” And the comfort of “fine” and certainty seemed better than the unknown.
And then it happened.
That whisper turned into a very hard and abrupt shove into another lane, as if I didn’t get the hint the first time.
I could have taken it as a punishment for not being one hundred percent happy with where I was at, and, I suppose I did for a while. But now, I know it was the universe trying to tell me something, and it wasn’t whispering anymore.
The universe was now yelling at me, loudly.
The lane-changer happened the day I discovered my husband of seventeen years had been cheating on me with another man.
The life I knew—the life that I was happy enough with—was gone in an instant on a hot, sweaty July day.
I did not handle it gracefully. I was an utter hot mess for months and months. The better part of a couple of years, really.
But I made it through the other side into my “new lane.” and I want to share a little bit about what helped me get here, and what helped me be truly happy here.
The reason I was so devastated when I was thrust into my new lane is that I had been clinging to this vision of the life I thought that I should be living—the life that was “normal.”
I was attached to so much—having a husband, having children, having a home, doing married-people-with-kids things. I could have never imagined my life a different way. In fact, it was scary to imagine my life differently.
As I got older, my world shrunk. My comfort zone got bigger.
When the crisis with my marriage happened, I tried to hold on tightly to everything that had just crumbled in front of me. But there was nothing left to hold on to –I was experiencing complete groundlessness.
That attachment to the way things had been was all I had. I didn’t have a ton of self-love, or “I’m okay on my own” mentality. My identity was “we” with my partner for nearly twenty years, and I didn’t know how to function as a “me.”
I had taken the little things, and the big things for granted.
So what helped me survive this?
Someone asked me this after I was feeling like my life was back on track, and after really thinking hard about it, three things came to me.
Gratitude, mindfulness, and self-love.
I’m often amazed at how succinctly I was able to boil down these lessons into a few things that were the tipping point for me to find myself, and my happiness again.
Start with Gratitude
Focusing on what we are grateful for is a super-simple and powerful tool that is often overlooked. We have access to gratitude at all times, and it is absolutely free. How’s that for a deal?
Practicing gratitude on the regular has a ton of benefits. Focusing on what you’re grateful for has been shown to increase self-esteem, make us less self-centered, improves health, helps us sleep better, improves our relationships, and… gratitude makes us happier. Boom!
Remember, gratitude is a practice. The more you cultivate it, the more you will feel it. Stick with it and try these simple ideas:
1. Make the decision to be grateful. It all starts here.
2. Keep a gratitude journal. Putting pen to paper (or a gratitude journal app if that’s more your speed) is a great way to get in the habit of focusing on the good things in your life, rather than the not-so-good things. Aim to write down at least 3 things you are grateful for every day.
There are other neat ways to do this too, such as sharing something you’re grateful for at the dinner table each evening, or keeping a gratitude jar, in which you write what you’re thankful for on slips of paper and drop them in the jar.
3. Create visual reminders of things you’re grateful for. Maybe a vision board? Or just a journal filled with images you love. If you’re an artist (or even if you’re not!), an art journal can be fun!
4. Think of ways you can show your gratitude in everyday life, like doing something nice for a homeless person because you are grateful to have a roof over your head
5. Think about how you can be grateful for the setbacks you’ve had—it’s hard, I know, but I promise you can find a silver lining in anything if you try! Journal about them.
6. Think about how you’d feel without something. How would you feel if you had ZERO family or friends? Or if you hate your job, how would you feel if you didn’t have a paycheck?
Next, Practice Mindfulness
I know, I know. Everyone talks about how mindfulness will help you be happier.
That’s because it works.
The benefits of practicing mindfulness are many. Personally, in terms of the quest for happiness, I think the greatest thing that you can learn being mindful is how to observe your thoughts without judging them.
Have you ever tried meditating, and found thoughts popping in and out of your head like a whack-a-mole game? And, if you’ve been in that space, have you been hard on yourself for not being able to meditate “properly”?
There is not a right or wrong way to meditate. You will have thoughts that pop into your head and that’s the way it’s supposed to be. The point is to notice the thoughts and let them be there without any judgment (good or bad).
Starting to pay attention and notice your thoughts is a huge step toward seeing which thoughts and patterns are getting in the way of your happiness. And then, once you begin to notice those thoughts and patterns, you can start to form new ones that will better serve you on your quest for happiness.
Finally, Treat Yourself Like You’d Treat Someone You Love
Once you’ve become more mindful of your thoughts, you might notice that your inner critic can be quite nasty sometimes, telling you you’re not _______ enough or not worthy enough.
Chances are, you’d never speak that way to your children, best friend, or partner. So why on earth do we say such horrible things to ourselves?
Think about it this way: Your inner critic has a lot of information that it has assimilated over the many years of your life. Some of it is helpful, and some of it just isn’t.
I used to hate my body. I was not nice to myself at all.
One day, it occurred to me that I would never say the things I said to myself to my daughter, and as someone who spent much of my adult life struggling with an eating disorder, I certainly did not want to pass that on to her.
I committed that day to work on talking to myself like I would talk to my daughter. To caring for myself like I would care for my daughter.
That started with telling myself I was worth self-love and self-care.
The second step was noticing when my inner critic was telling me that I was not worth that love and care. Once I was able to notice those thoughts, I was able to start replacing them with more helpful thoughts and words.
Is any of this going to happen overnight?
Nope.
Happiness is something we all spend an awful lot of time looking for, and this feeling of peace and contentment that we all hunger for seems pretty elusive sometimes. But remember, it is in you. You already have everything you need inside of you. These three practices are some pretty simple things that you can do to start your journey toward happiness using what is already inside you.
Everything is a process. You don’t get from point A to point B overnight. It’s the little things that you take the time to do every day that get you there. If you stare at a blade of grass, you can’t see it growing minute-by-minute, but when your lawn needs to be mowed, you can be pretty sure it grew a lot!
The end result will come, but you must have patience. You must be grateful for the process to learn and grow. And during the process, you must treat yourself with love, kindness, and respect.
When you can embrace this truth, you are sure to end up in a beautiful place, and one day, you too, will live from a place of happiness, purpose, and fulfillment.
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HBD X HPPY CONTINUATION DAY , THAY
Together we continue Thay
In this post, we share more stories from our monastic brothers and sisters as well as stories of transformation selected from our friends who have offered their stories as a gift to Thich Nhat Hanh (Thay) as we continue to celebrate Thay’s 94th continuation day.
As a manifold sangha, we can continue and spread Thay’s legacy of engaged Buddhism. Sr Dieu Nghiem (an elder monastic, also affectionately known as Sr Jina) often shares that the monastic brothers and sisters are like the palm of the hand, and the lay sanghas are like the fingers on the hand. Without the fingers, the hand cannot do much, and without the palm the fingers would not have a structure to be able to do anything. We inter-are, and we are there to support one another. The lay sanghas are like an extension of the palm, helping to bring the Dharma far and wide to places that the monastic sangha may not be able to reach. As the monastic sangha, we are there for you as a refuge where you can learn about the practices, resource and heal yourself in order to continue your bodhisattva work with us.
Letter from Brother Đạo Bi
Dear respected Thay,
My name is Chân Trời Đạo Bi. I received novice ordination at Wihara Ekayana Arama, Jakarta, Indonesia in May 2015. Before ordaining I had already wanted to become your disciple, but due to some causes and conditions I ordained in Indonesia with my teacher, whom I feel a deep affinity with and who supported me to receive full ordination at Plum Village in February 2019. My teacher and I have a dream of renewing Buddhism in Indonesia, and because we see that Thay has been able to do so, we know it is possible. When I received a lineage name – True Sky over the Path of Compassion, I felt very happy. The Path of Compassion is one of my favorite chapters in your book “Old Path White Cloud” that I read over and over.
Dear Thay, I first met you at a retreat in Indonesia in September 2010. At the end of the retreat I felt a strong desire to become vegetarian. I received the Five Mindfulness Trainings and have been vegetarian since then. Initially my parents didn’t support me to become vegetarian, but as they saw my transformation, my mother decided by herself to become vegetarian a few years later. I think it happened because she saw how my health has improved a lot after losing about 20 kilos. I used to eat a lot of junk food, so I accumulated a lot of toxins and tension in my body. Since I came to Plum Village I have learned to eat in a healthier way, and that what I need to eat is only half of what I used to eat before. Slowly I feel lighter in my body, and it has improved the quality of my practice, in particular sitting meditation.
Dear Thay, I have seen how effective the tools of deep listening and loving speech are in restoring communication in my blood family. I studied communication at university, but it didn’t help me to restore communication with others much. My parents often argued with me, telling me to stop being vegetarian. After trying to reason with them for some months, I felt that it wasn’t effective because they wouldn’t listen. So I decided to practice deep listening whenever they argued or got angry with me. After some years, my mother noticed the transformation in me. She was curious and then started to learn the Dharma. I gave her some of Thay’s books and other Dharma books. When my father got angry, together we could listen to him and it changed the atmosphere in my family a lot.
I feel very happy that I can help my mother get in touch with the Dharma. Sometimes I regret that I couldn’t help my father to get in touch with the Dharma before he died. Yet I know just by practicing deep listening, my mother and I already helped him to relieve his suffering. Sometimes when I practice sitting or walking meditation, and I feel light and free, I ask my father and mother inside me, “Do you feel light and free?” I find this guided meditation very helpful for reconciling with my father in me and get a lot of healing from it.
Dear Thay, sometimes I share my dream of renewing Buddhism in Indonesia with others. But then I asked myself, “Who am I to have such an ambitious dream of renewing Buddhism in my country?” In Thay’s letter for the monastic brothers and sisters, he said that if you want to renew Buddhism, you have to renew yourself first. Dear Thay, I have shared with you my practice of renewing myself in this letter. I’m still a very young monk, and I still need to learn many things and practice to renew myself in many aspects.
I’m deeply grateful to my parents, teachers, friends, and all beings who give guidance and support along the path. Dear Thay, I am aware that I owe so much to you, who shows me the way in this life. I vow to be worthy of your trust and to practice wholeheartedly. Br Chân Trời Đạo Bi
The precious breath, the healing breath
My baby Thomas was unexpectedly born with a rare respiratory disease. I lived in the NICU (neonatal intensive care unit) with him, holding and comforting him day and night. I was compelled to place Thay’s book, Peace In Every Step, in the large crib alongside the medical equipment. The simple presence of this powerful book offered me a sense of peace. These many weeks living in the hospital with baby Thomas was like a retreat. My focus was on witnessing each labored breath my baby took. The sacredness of each breath and each moment came alive for me in this painful yet beautiful way. Thank you, Thay, for teaching me to breathe, to appreciate, and to love. Lisa
Dear Thay and dear friend reading my words at this present moment, this beautiful moment, thank you for giving me the opportunity to reflect on my journey towards compassion through your wonderful gift to the world of continuing to breathe.
I cannot say when the first seed from the garden of your practice took root in my mind.
I can remember a beautiful flowering of one such seed when, as a young woman I suffered a life threatening illness leading to long term, but not permanent, disability when I practiced breathing mindfully and paying compassionate attention to my sensations of physical pain.
I can recall years later far more difficult psychological pain when I caused myself to suffer greatly through unwise attachment. Plum Village meditation tapes and CDs brought your wisdom to me.
Today in these times of pandemic I am blessed by connection with nature and the spiritual resources I have gathered on my journey towards compassion. When my dear father was dying from Covid pneumonia in April I was able to be with him in spirit and thanks to the dear nurses make connections through technology so that many family members were able to communicate with him in his final hours. The dear doctors and nurses were our hands and hearts. Interbeing.
I was privileged to discover a small ministry of compassionate support attempting with every communication to give appreciation and listen to the pain of all those so deeply affected by the pandemic seeing so many of their patients dying.
May every breath draw me near to that perfect compassion and inner peace of which you are a most beloved teacher. 🙏🏽 Clare
Dearest Thay,
One night I was on my way out when I tripped and fell, hitting my head on a door frame. The pain was intense, and blood began pooling on the floor beside me. I held a towel to my head but the bleeding continued as unbeknownst to me, I had also split my ear open. I was home alone, in pain, frightened, and my heart racing at the thought of not being able to stop the bleeding. I rang for the ambulance and sat on the floor by the front door waiting.
I closed my eyes and I heard your calm and loving voice in my head, “Hello pain, I see you there. I am here for you. I will take care of you” and in that moment, my heart rate slowed, the pain decreased and I was calm.
Thank you for teaching me how to care for myself and all beings with love and kindness.
Blessings to you on your Continuation Day dear Thay. You are a true gift to us all.
Love and Peace, Kerryn
Deep listening and loving speech
A few years ago my sister and I had a talk which turned into an argument. I heard her say a sentence about me and understood it in one way. I told her what I had understood and she insisted it was not what she had meant to say.
We stopped talking to each other, only when it was absolutely necessary and only on that specific subject. It went on for a few months. In one occassion we were invited to a family gathering, each came on her own and we did not speak to each other. Family members tried to reconcile us with no success. She insisted at that time that I put words into her mouth and interpretations that were not hers and it was totally my problem. It was very difficult to live during the time that we did not speak to each other. She broke her leg and I was not there for her, We went through times where a close uncle passed away yet we could not reconcile with one another.
I have belonged to the Tel Aviv Sangha for about seven years.
I listen to and practice Thay’s teachings yet I could not overcome my mishap with my sister. Until one day I listened to a talk in the Sangha about ideas that may not seem as they truly are. Looking at them from a different perspective – from the suffering of inner self, and BAM! it happened.
I thought about what my sister said and how she had said it and understood that I was wrong all this time. I had misunderstood her and knew that I had to fix it immediately.
So I called her and asked her to meet and apologized for having misinterpreted her meanings. She told me she highly respects what I am doing right now and she knows it is not easy and she is proud of me. (Actually it was much easier than she thought and it came with instant relief).
We reconciled. There is still a heavy air between us since we do not fully trust one another, yet we are back to being sisters, setting an example to our family and friends how to react in difficult times, sticking together.
Thank you Thay from the bottom of my heart and soul for this and many more lessons.
Many continuation days,
Please know that you have impacted and transformed many lives around the globe and will continue doing so through the Sanghas spread around the world, forever.
Vered, Matan, Israel
Your phrase “My darling, I am suffering and I need your help” truly did save my marriage. I had been responding to disagreements with my husband with the equivalent of “I am suffering and it is your fault.” I first used your healing words without much faith, in desperation because we had caused each other so much pain that we were on the verge of divorce. As soon as I said them, a miracle happened for us: there was a shift from a painful cycle of hurt and counter-hurt to one with room for gentle curiousness and concern. With the help of the teachings contained in these words – that my husband and I inter-are, that we need each other’s help—we have become supportive friends to one another for many years. Your words help us to work together to transform suffering when it arises between us. You have taught me that deep listening means helping the beloved to truly feel heard: I was able to understand that my husband needed to be listened to in a way very differently than I do: while I do not like to be interrupted, he feels interruptions show my interest and understanding. You have taught us both to not speak when angry but to wait until we can use skillful speech again. Dannah
Beloved Thay, Beloved Sangha,
A blessed continuation dear Thay.
Every day when I meditate, feel the earth breathing in me, you Thay, are present with me.
Every day when I relax into the stillness, dear Thay, I am with you. Every moment you whisper stop, breathe, stay with awareness, you are alive in me and
I am alive in you.
I remember your words, we rely on each other to manifest. Without a child there is no father, without a teacher there is no disciple. We inter-are. There is no separate self.
I am alive in you, you are alive in me. The Sangha is alive in all of us, we are all cells of one organism. I bow for you, you breathe for me. Together we awaken. I love you.
Chan Tue Chau
True Jewel of Understanding
Daily practice
For each day that I struggle with my own humanness, I am given another day to reach out and assist others. The beautiful unpretentious teaching Thay has offered for so long is a simple thread to grasp, yet a mouthwatering taste of peace and joy. I refer to his writings often when writing Sunday talks or responding to those who have reached out to me. And so for this auspicious birthday, I offer this reflection in Haiku.
My practice is weak
but my heart soars knowing Truth
is setting me free.
When I stumble now
loving wisdom catches me
and whispers my name
What’s this in my heart?
Compassion! Filling me and
all living beings.
One day at a time
I am aware of my heart.
I breathe in and out.
Liliane
A few months after I was in an awful accident which changed my life, my friend, Sari Holmes, dragged me to St. John the Divine to hear Thich Nhat Hanh speak. Because I needed special seating, we were seated almost at his feet in the pews. Afterwards, as I was preparing to leave, I was approached by one of his aides. I was told he wanted to know how I felt. I was in a neck and shoulder brace, had been laying on the pew for most of his talk, and was using walking sticks at the time. I told him I don’t know what feelings are anymore. His next question was, “What makes you happy?” I responded, “Doing the dishes”. I was escorted to the gift shop and given a card of his artwork with three drawings and kitchen meditations on it. That card stayed on my refrigerator for almost twenty years. I’m pretty sure I stored it in my personal memorabilia box, yet since moving to Oregon, I’ve been unable to find it. Still, everyday, I follow the instructions I was given and remain happy in the now.
If what he did for me was the same for all of us who treasured his being, he will not be forgotten. Happy 94th Continuation Day.
Margie
Sister Trang Mai Thon shares her practice…
When I was newly ordained a few months, I had many opportunities to eat lunch with Thay at the Hermitage. He would say to me, “You should write a book about your life, and Thay will write the foreword.” I just smiled. Later on, I found out that Thay had encouraged many other brothers and sisters to do the same. In fact, at the time I thought that Thay could see how much suffering I had, and encouraged me to use writing as a means to heal myself. It is because while writing we have the opportunity to reflect on what has happened and what is happening in our body and mind, and through this process we can heal a lot of wounds. Writing to Thay has helped me to heal a lot. In the first few years I often wrote to Thay sharing with him whatever little progress I had made in the practice, my difficulties and what I did to try and overcome them, or what obstacles I was encountering. I already had an elder sister as a mentor and I wrote in my “công phu” book of my daily practice to give to her. But Thay was my “underground mentor”, and he could read what was most secret in my heart.
Thay said to me, “Sr Mai Thon, now all you need to do is to live joyfully, you don’t need to do anything more”. In the years that I have stayed in Plum Village, I have practiced to live joyfully, and have grown up nourished gradually by the joy from Thay and the sangha. I hope that I too have nourished Thay and the sangha by my own simple practice of following the sangha and the schedule, by my practice of being an obedient young novice observing the precepts and find manners. Whatever I learnt, I put it into practice. I enjoyed the simple things in life, allowed myself to enjoy the happiness of my sisters around me. There were times I felt reluctant to join others, but encouraged myself to do so. Every time I made an effort to overcome the tendency to withdraw, I felt a little more joy. I also practiced to recognize my habit of reacting and tried to stop more often.
Every year we receive many lay friends for our Christmas retreat. They come for many reasons. Some come alone, others with their parent(s), and some even bring their whole family. Last year I spoke with a lady from a Christian background who came to Plum Village because she had just lost her husband of 28 years. She could not accept this loss because it happened suddenly. She didn’t want to celebrate Christmas with her family because she was afraid that her sadness would affect them too much, so that was why she came to Plum Village. In my life I have gone through many losses of loved ones. Sometimes the loss came unexpectedly and I could not accept it. I held on to that pain for many years until fortunately, I heard Thay’s Dharma talk about the peach blossom blooming too early when the weather suddenly warmed up in the middle of winter. It thought that spring had arrived, but when the weather became cold again it fell to the earth. Six years ago when Thay had a stroke, he gave us an opportunity to practice facing impermanence through the possibility of “losing Thay”. Thanks to all these experiences that I was able to share with this friend and inspire her to see that she has not lost her husband. In fact, he has never left her.
I practice to see Thay in my fellow practitioners. Sometimes I ask myself how I can I feel close to and love these people like that? We come from the ten directions with different languages, habits, and cultures, and yet we can live together, love and accept each other. When someone leaves the monastic sangha I feel sad as if I’ve lost a loved one. During one sitting meditation I realized that if we did not share a common aspiration; if we didn’t have the same practices; if we did not keep the precepts then if we had met each other we would have nothing to talk about. We would not have a common language to communicate with each other. This was very clear to me. There are monastics from other traditions who visit to take refuge in Thay and end up joining the Plum Village sangha. I treasure them very much and feel very close to them. I feel comfortable with them and can trust them. This is because we have a common language – the mindfulness practices, our monastic precepts, our shared aspirations and the sangha.
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I experience pain, I don’t suffer it. Experience is enough.
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BG 11.54: O Arjun, by unalloyed devotion alone can I be known as I am, standing before you. Thereby, on receiving my divine vision, O scorcher of foes, one can enter into union with me.
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EMOTIONS ARE GUESSES
EXPERIENTIAL BLINDNESS
PREDICTIONS ARE THE WAY YR BRAIN WORKS
PREDICTIONS ARE PRIMAL
TED -LISA FREDMANN BARRETT
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Onward, Forward, Godward |
REALISE IT YOURSELF
How can I describe that exalted state? It cannot be written on paper, It cannot be told in words, There is no language To describe that state. Language is imperfect. Can you explain colour To a blind man? It is like that state Of a dumb person Who tastes a sweet thing. How can it be explained? You will have to realise it yourself: Thus sayeth Sivananda. |
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Baby Bottles Release Millions of Microplastic Parts
Now, when a jury has to make the decision between life in prison and the death penalty, they base their decision largely on whether or not the defendant feels remorseful for his actions. Tsarnaev spoke words of apology, but when jurors looked at his face, all they saw was a stone-faced stare. Now, Tsarnaev is guilty, there's no doubt about that. He murdered and maimed innocent people, and I'm not here to debate that. My heart goes out to all the people who suffered. But as a scientist, I have to tell you that jurors do not and cannot detect remorse or any other emotion in anybody ever. Neither can I, and neither can you, and that's because emotions are not what we think they are. They are not universally expressed and recognized. They are not hardwired brain reactions that are uncontrollable. We have misunderstood the nature of emotion for a very long time, and understanding what emotions really are has important consequences for all of us.
I have studied emotions as a scientist for the past 25 years, and in my lab, we have probed human faces by measuring electrical signals that cause your facial muscles to contract to make facial expressions. We have scrutinized the human body in emotion. We have analyzed hundreds of physiology studies involving thousands of test subjects. We've scanned hundreds of brains, and examined every brain imaging study on emotion that has been published in the past 20 years. And the results of all of this research are overwhelmingly consistent. It may feel to you like your emotions are hardwired and they just trigger and happen to you, but they don't. You might believe that your brain is prewired with emotion circuits, that you're born with emotion circuits, but you're not. In fact, none of us in this room have emotion circuits in our brain. In fact, no brain on this planet contains emotion circuits.
Now, if that sounds preposterous to you, or, you know, kind of crazy, I'm right there with you, because frankly, if I hadn't seen the evidence for myself, decades of evidence for myself, I am fairly sure that I wouldn't believe it either. But the bottom line is that emotions are not built into your brain at birth. They are just built.
To see what I mean, have a look at this. Right now, your brain is working like crazy. Your neurons are firing like mad trying to make meaning out of this so that you see something other than black and white blobs. Your brain is sifting through a lifetime of experience, making thousands of guesses at the same time, weighing the probabilities, trying to answer the question, "What is this most like?" not "What is it?" but "What is this most like in my past experience?" And this is all happening in the blink of an eye. Now if your brain is still struggling to find a good match and you still see black and white blobs, then you are in a state called "experiential blindness," and I am going to cure you of your blindness. This is my favorite part. Are you ready to be cured?
All right. So now many of you see a snake, and why is that? Because as your brain is sifting through your past experience, there's new knowledge there, the knowledge that came from the photograph. And what's really cool is that that knowledge which you just acquired moments ago is changing how you experience these blobs right now. So your brain is constructing the image of a snake where there is no snake, and this kind of a hallucination is what neuroscientists like me call "predictions." Predictions are basically the way your brain works. It's business as usual for your brain. Predictions are the basis of every experience that you have. They are the basis of every action that you take. In fact, predictions are what allow you to understand the words that I'm speaking as they come out of my --
The way that we see emotions in others are deeply rooted in predictions. So to us, it feels like we just look at someone's face, and we just read the emotion that's there in their facial expressions the way that we would read words on a page. But actually, under the hood, your brain is predicting. It's using past experience based on similar situations to try to make meaning. This time, you're not making meaning of blobs, you're making meaning of facial movements like the curl of a lip or the raise of an eyebrow. And that stone-faced stare? That might be someone who is a remorseless killer, but a stone-faced stare might also mean that someone is stoically accepting defeat, which is in fact what Chechen culture prescribes for someone in Dzhokhar Tsarnaev's situation.
are spending millions of research dollars to build emotion-detection systems, and they are fundamentally asking the wrong question, because they're trying to detect emotions in the face and the body, but emotions aren't in your face and body. Physical movements have no intrinsic emotional meaning. We have to make them meaningful. A human or something else has to connect them to the context, and that makes them meaningful. That's how we know that a smile might mean sadness and a cry might mean happiness, and a stoic, still face might mean that you are angrily plotting the demise of your enemy. Now, if I haven't already gone out on a limb, I'll just edge out on that limb a little further and tell you that the way that you experience your own emotion is exactly the same process. Your brain is basically making predictions, guesses, that it's constructing in the moment with billions of neurons working together.
Now your brain does come prewired to make some feelings, simple feelings that come from the physiology of your body. So when you're born, you can make feelings like calmness and agitation, excitement, comfort, discomfort. But these simple feelings are not emotions. They're actually with you every waking moment of your life. They are simple summaries of what's going on inside your body, kind of like a barometer. But they have very little detail, and you need that detail to know what to do next. What do you about these feelings? And so how does your brain give you that detail? Well, that's what predictions are. Predictions link the sensations in your body that give you these simple feelings with what's going on around you in the world so that you know what to do. And sometimes, those constructions are emotions.
So for example, if you were to walk into a bakery, your brain might predict that you will encounter the delicious aroma of freshly baked chocolate chip cookies. I know my brain would predict the delicious aroma of freshly baked chocolate cookies. And our brains might cause our stomachs to churn a little bit, to prepare for eating those cookies. And if we are correct, if in fact some cookies have just come out of the oven, then our brains will have constructed hunger, and we are prepared to munch down those cookies and digest them in a very efficient way, meaning that we can eat a lot of them, which would be a really good thing.
But here's the thing. That churning stomach, if it occurs in a different situation, it can have a completely different meaning. So if your brain were to predict a churning stomach in, say, a hospital room while you're waiting for test results, then your brain will be constructing dread or worry or anxiety, and it might cause you to, maybe, wring your hands or take a deep breath or even cry. Right? Same physical sensation, same churning stomach, different experience.
And so the lesson here is that emotions which seem to happen to you are actually made by you. You are not at the mercy of mythical emotion circuits which are buried deep inside some ancient part of your brain. You have more control over your emotions than you think you do. I don't mean that you can just snap your fingers and change how you feel the way that you would change your clothes, but your brain is wired so that if you change the ingredients that your brain uses to make emotion, then you can transform your emotional life. So if you change those ingredients today, you're basically teaching your brain how to predict differently tomorrow, and this is what I call being the architect of your experience.
So here's an example. All of us have had a nervous feeling before a test, right? But some people experience crippling anxiety before a test. They have test anxiety. Based on past experiences of taking tests, their brains predict a hammering heartbeat, sweaty hands, so much so that they are unable to actually take the test. They don't perform well, and sometimes they not only fail courses but they actually might fail college. But here's the thing: a hammering heartbeat is not necessarily anxiety. It could be that your body is preparing to do battle and ace that test ... or, you know, give a talk in front of hundreds of people on a stage where you're being filmed.
And research shows that when students learn to make this kind of energized determination instead of anxiety, they perform better on tests. And that determination seeds their brain to predict differently in the future so that they can get their butterflies flying in formation. And if they do that often enough, they not only can pass a test but it will be easier for them to pass their courses, and they might even finish college, which has a huge impact on their future earning potential. So I call this emotional intelligence in action.
Now you can cultivate this emotional intelligence yourself and use it in your everyday life. So just, you know, imagine waking up in the morning. I'm sure you've had this experience. I know I have. You wake up and as you're emerging into consciousness, you feel this horrible dread, you know, this real wretchedness, and immediately, your mind starts to race. You start to think about all the crap that you have to do at work and you have that mountain of email which you will never dig yourself out of ever, the phone calls you have to return, and that important meeting across town, and you're going to have to fight traffic, you'll be late picking your kids up, your dog is sick, and what are you going to make for dinner? Oh my God. What is wrong with your life? What is wrong with my life?
That mind racing is prediction. Your brain is searching to find an explanation for those sensations in your body that you experience as wretchedness, just like you did with the blobby image. So your brain is trying to explain what caused those sensations so that you know what to do about them. But those sensations might not be an indication that anything is wrong with your life. They might have a purely physical cause. Maybe you're tired. Maybe you didn't sleep enough. Maybe you're hungry. Maybe you're dehydrated. The next time that you feel intense distress, ask yourself: Could this have a purely physical cause? Is it possible that you can transform emotional suffering into just mere physical discomfort?
Now I am not suggesting to you that you can just perform a couple of Jedi mind tricks and talk yourself out of being depressed or anxious or any kind of serious condition. But I am telling you that you have more control over your emotions than you might imagine, and that you have the capacity to turn down the dial on emotional suffering and its consequences for your life by learning how to construct your experiences differently. And all of us can do this and with a little practice, we can get really good at it, like driving. At first, it takes a lot of effort, but eventually it becomes pretty automatic.
Now I don't know about you, but I find this to be a really empowering and inspiring message, and the fact that it's backed up by decades of research makes me also happy as a scientist. But I have to also warn you that it does come with some fine print, because more control also means more responsibility. If you are not at the mercy of mythical emotion circuits which are buried deep inside your brain somewhere and which trigger automatically, then who's responsible, who is responsible when you behave badly? You are. Not because you're culpable for your emotions, but because the actions and the experiences that you make today become your brain's predictions for tomorrow. Sometimes we are responsible for something not because we're to blame but because we're the only ones who can change it.
Now responsibility is a big word. It's so big, in fact, that sometimes people feel the need to resist the scientific evidence that emotions are built and not built in. The idea that we are responsible for our own emotions seems very hard to swallow. But what I'm suggesting to you is you don't have to choke on that idea. You just take a deep breath, maybe get yourself a glass of water if you need to, and embrace it. Embrace that responsibility, because it is the path to a healthier body, a more just and informed legal system, and a more flexible and potent emotional life.
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