Persistent organic pollutants-environmental risk factors for diabetes mellitus? - A population-based study.

BACKGROUND: Globally, type-2 diabetes mellitus is increasing in epidemic proportions. A major cause of concern in India is the increasing incidence of cases, especially troubling is the observed increase in younger age groups with no risk factors. New evidence suggests that many environmental factors, such as air pollution, persistent organic pollutants (POPs), and environmental estrogens are implicated as risk factors for type-2 diabetes mellitus. Animal and human epidemiological studies have shown ubiquitous lipophilic substances, including POPs, are frequently associated with type-2 diabetes mellitus. Such studies have not been undertaken in Indian youth. METHODS: This is a cross-sectional study that explored the association between POPs and type-2 diabetes mellitus in Indian urban and rural population. About 7 ml of venous blood was collected from all consenting patients and serum was separated immediately and was transported to the lab for further analysis. Serum levels of POPs, including organochlorine (OC) compounds and organophosphorus pesticides, were estimated using sample gas chromatography-mass spectrometry (GC-MS). The fasting blood sugar values and the serum levels of POPS were tested using Pearson correlation coefficient. The magnitude of increase in blood sugar corresponding to increase in POPs was analyzed using linear regression analysis. The odds ratios (ORs) were expressed at 95% confidence intervals (CIs). RESULTS: Three OC pesticides and one organophosphate pesticide were strongly associated with increasing blood sugar levels after adjusting for age, sex, and body mass index - lindane (OR 4.95, 95% CI 1.03-23.73), DDT o, p' (OR 3.50, 95% CI 1.04-11.73), dimethoate (OR 19.31, 95% CI 4.22-88.37), and dichlorvas (OR 6.33, 95% CI 1.28-31.18).

Neighborhood Exposures and Blood Pressure Outcomes: A Cross-Sectional Environmental Study among 19-53 Years-Old Parsis in Mumbai.

The correlation between high blood pressure (BP) and urban neighborhood-level environmental determinants is understudied in low-income and middle-income countries (LMICs). We hypothesized that neighborhoods constitute exposures that affect resident-behaviors, metabolism and increased susceptibility to high BP. We studied urban clusters of Mumbai-Parsis (Zoroastrians), a founder population group, to minimize genetic variation and maximize exposure assessment. Participants from four neighborhoods were 19-53 years old and comprised 756 females and 774 males. We recorded healthy BPs (≤120/80 mmHg) in 59%, pre-hypertensive (≥121-139/81-89 mmHg) in 21% and high BP (≥140/90 mmHg) in 21% of the participants. A family history of hypertension had no correlation with high BP. We used the Neighborhood Accessibility Framework to compile a questionnaire in order to collect data on participants' perception of space, third places, streetscape and experience, land use, connectivity, surveillance, pedestrian safety and public transport. Our results suggested that participants in neighborhoods with poorer BP outcomes reported lower accessibility scores for space, streetscape and experience, third places and connectivity. Our study evaluates how neighborhood-level determinants affect BP outcomes in order to contribute to the body of knowledge on primary preventive measures for high BP in urban LMIC populations. We concluded that neighborhood exposures affect resident-behaviors, which cause metabolic changes and increase susceptibility to high BP.

Predicting Fatigue in Long Duration Mountain Events with a Single Sensor and Deep Learning Model.

AIM: To determine whether an AI model and single sensor measuring acceleration and ECG could model cognitive and physical fatigue for a self-paced trail run. METHODS: A field-based protocol of continuous fatigue repeated hourly induced physical (~45 min) and cognitive (~10 min) fatigue on one healthy participant. The physical load was a 3.8 km, 200 m vertical gain, trail run, with acceleration and electrocardiogram (ECG) data collected using a single sensor. Cognitive load was a Multi Attribute Test Battery (MATB) and separate assessment battery included the Finger Tap Test (FTT), Stroop, Trail Making A and B, Spatial Memory, Paced Visual Serial Addition Test (PVSAT), and a vertical jump. A fatigue prediction model was implemented using a Convolutional Neural Network (CNN). RESULTS: When the fatigue test battery results were compared for sensitivity to the protocol load, FTT right hand (R2 0.71) and Jump Height (R2 0.78) were the most sensitive while the other tests were less sensitive (R2 values Stroop 0.49, Trail Making A 0.29, Trail Making B 0.05, PVSAT 0.03, spatial memory 0.003). The best prediction results were achieved with a rolling average of 200 predictions (102.4 s), during set activity types, mean absolute error for 'walk up' (MAE200 12.5%), and range of absolute error for 'run down' (RAE200 16.7%). CONCLUSIONS: We were able to measure cognitive and physical fatigue using a single wearable sensor during a practical field protocol, including contextual factors in conjunction with a neural network model. This research has practical application to fatigue research in the field.

Moving the Lab into the Mountains: A Pilot Study of Human Activity Recognition in Unstructured Environments.

GOAL: To develop and validate a field-based data collection and assessment method for human activity recognition in the mountains with variations in terrain and fatigue using a single accelerometer and a deep learning model. METHODS: The protocol generated an unsupervised labelled dataset of various long-term field-based activities including run, walk, stand, lay and obstacle climb. Activity was voluntary so transitions could not be determined a priori. Terrain variations included slope, crossing rivers, obstacles and surfaces including road, gravel, clay, mud, long grass and rough track. Fatigue levels were modulated between rested to physical exhaustion. The dataset was used to train a deep learning convolutional neural network (CNN) capable of being deployed on battery powered devices. The human activity recognition results were compared to a lab-based dataset with 1,098,204 samples and six features, uniform smooth surfaces, non-fatigued supervised participants and activity labelling defined by the protocol. RESULTS: The trail run dataset had 3,829,759 samples with five features. The repetitive activities and single instance activities required hyper parameter tuning to reach an overall accuracy 0.978 with a minimum class precision for the one-off activity (climbing gate) of 0.802. CONCLUSION: The experimental results showed that the CNN deep learning model performed well with terrain and fatigue variations compared to the lab equivalents (accuracy 97.8% vs. 97.7% for trail vs. lab). SIGNIFICANCE: To the authors knowledge this study demonstrated the first successful human activity recognition (HAR) in a mountain environment. A robust and repeatable protocol was developed to generate a validated trail running dataset when there were no observers present and activity types changed on a voluntary basis across variations in terrain surface and both cognitive and physical fatigue levels.

Psychophysiological assessment and correction of spatial disorientation during simulated Orion spacecraft re-entry.

The National Aeronautics and Space Administration (NASA) has identified a potential risk of spatial disorientation, motion sickness, and degraded performance to astronauts during re-entry and landing of the proposed Orion crew vehicle. The purpose of this study was to determine if a physiological training procedure, Autogenic-Feedback Training Exercise (AFTE), can mitigate these adverse effects. Fourteen men and six women were assigned to two groups (AFTE, no-treatment Control) matched for motion sickness susceptibility and gender. All subjects received a standard rotating chair test to determine motion sickness susceptibility; three training sessions on a manual performance task; and four exposures in the rotating chair (Orion tests) simulating angular accelerations of the crew vehicle during re-entry. AFTE subjects received 2 h of training before Orion tests 2, 3, and 4. Motion sickness symptoms, task performance, and physiological measures were recorded on all subjects. Results showed that the AFTE group had significantly lower symptom scores when compared to Controls on test 2 (p = .05), test 3 (p = .03), and test 4 (p = .02). Although there were no significant group differences on task performance, trends showed that AFTE subjects were less impaired than Controls. Heart rate change scores (20 rpm minus baseline) of AFTE subjects indicated significantly less reactivity on Test 4 compared to Test 1 (10.09 versus 16.59, p = .02), while Controls did not change significantly across tests. Results of this study indicate that AFTE may be an effective countermeasure for mitigating spatial disorientation and motion sickness in astronauts.

CT angiography to evaluate coronary artery disease and revascularization requirement before trans-catheter aortic valve replacement.

BACKGROUND: Coronary artery disease (CAD) and aortic stenosis share pathophysiological mechanisms and risk factors. We evaluated the clinical utility of coronary computed tomography angiography (CTA) to identify CAD and revascularization requirement in patients with severe aortic stenosis considered for transcatheter aortic valve replacement (TAVR). METHODS: Consecutive patients without known CAD underwent calcium scoring, CTA and invasive coronary angiography (ICA). A second-generation dual-source CT scanner was used. ICA-quantitative coronary angiography (QCA) served as reference standard. CAD was reported using a lenient threshold of ≥50% and a stricter threshold of ≥70% diameter reduction. Findings of ≥70% diameter reduction and of high-risk CAD were used to predict revascularization. RESULTS: The study included 140 patients [68 males; 82.3 (7.7) years]. CAD defined by the 50% threshold on ICA was found in 58/140 (41%) patients. CAD by the 70% threshold was found in 23/140 (16%) patients. High-risk CAD was found in 16/140 (11%) patients. CTA and ICA had similar odd-ratios of 3.22 (1.26-8.23) and 4.62 (1.64-13.05), respectively, in predicting revascularization. Forty-two/140 (30%) patients had <400 Agatston calcium score, 98/140 (70%) patients had ≥400 calcium score. The diagnostic performance of CTA in the low calcium score group was better than the high calcium score group (AUC 0.81 vs. 0.63). CONCLUSION: CTA remained questionable to rule-out CAD as gatekeeper to ICA in TAVR candidates who had severe coronary calcifications. In patients with less severe coronary calcifications, accounting for 30% of participants in this study, CTA may play a clinical role.

Fluid loading effects on temporal profiles of cardiovascular responses to head-down tilt.

BACKGROUND: Susceptibility of healthy astronauts to orthostatic hypotension and presyncope is exacerbated upon return from spaceflight. Up to 64% of astronauts experience postflight orthostatic intolerance. A promising countermeasure for postflight orthostatic intolerance is fluid loading by giving crew salt tablets and water prior to re-entry. The primary goal of the current study was to determine the optimal time window prior to re-entry when individual crew-persons would initiate fluid loading. METHODS: There were 16 subjects who were given two 6-h exposures, with and without fluid loading (conditions), to head-down tilt (HDT) to simulate the effects of microgravity. Pre- and post-HDT stand tests of orthostatic tolerance were given. Physiological measurements recorded included heart rate, blood pressure, peripheral blood volume, total peripheral resistance, and impedance cardiography. Echocardiography measures of stroke volume and cardiac output were also recorded. RESULTS: Data were analyzed with three-way repeated measures ANOVA (gender × condition × time). Only the condition × time interaction was significant for mean arterial pressure. Post hoc multiple comparison tests revealed significant increases in mean arterial pressure occurred between hours 1 and 3 of HDT after fluid loading (10 mmHg higher than no fluid). DISCUSSION: These findings indicate that the optimal time for crew to begin fluid loading is within 1 to 3 h prior to re-entry. Nonsignificant trends of multiple cardiovascular responses showed similar time profiles. The large amount of individual variability suggests that fluid loading alone may be an inadequate countermeasure for all crewmembers. Further research is needed on possible adjunct methods of tailoring countermeasures for individuals.

High levels of tobacco-specific N-nitrosamines and nicotine in Chaini Khaini, a product marketed as snus.

INTRODUCTION: Recently, a tobacco product, Chaini Khaini, identified as snus appeared in India. The product marketing emphasises its discreet nature and explicitly claims safety by referring to the existing evidence on Swedish snus. We analysed tobacco-specific nitrosamines and nicotine in 12 samples of Chaini Khaini purchased in 2013 at open markets in India. METHODS: Samples were purchased twice: in March 2013 from Mumbai and in November 2013 from Mumbai and Ahmedabad. Chemical constituents were measured by our routine validated methods. RESULTS: Levels of carcinogenic nitrosamines NNN, NNK and NNAL averaged 22.9 (±4.9), 2.6 (±1.0) and 3.1 (±1.5) µg/g tobacco (wet weight), respectively. The levels of NAB, which is normally present in trace levels in tobacco products, ranged from 3.9 to 12.9 µg/g tobacco. Total nicotine levels in all samples averaged 10.0 mg/g tobacco and unprotonated nicotine accounted for an average 95.4% of the total nicotine content. CONCLUSIONS: Chaini Khaini, which is labelled as snus and is marketed as a safe alternative to other tobacco products contains very high levels of carcinogenic nitrosamines and biologically available nicotine. Interventions are urgently needed to educate current and potential consumers of this product.

G-loading and vibration effects on heart and respiration rates.

BACKGROUND: Operational environments expose pilots and astronauts to sustained acceleration (G loading) and whole-body vibration, alone and in combination. Separately, the physiological effects of G loading and vibration have been well studied; both have effects similar to mild exercise. The few studies of combined G loading and vibration have not reported an interaction between these factors on physiological responses. METHODS: We tested the effects of G loading (+1 and +3.8 G(x)) and vibration (0.5 gx at 8, 12, and 16 Hz), alone and in combination, on heart and respiration rate. RESULTS: We observed an effect of G loading on heart rate (average increase of 23 bpm, SD 12) and respiration rate (average increase of 5 breaths per minute, SD 5), an effect of vibration on heart rate, and an interaction on heart rate. With vibration, we observed heart rate increases of 4 bpm (SD: 3) with no increase in respiration rate. In the +1 G(x) condition, the largest heart rate increase occurred during low-frequency (8 Hz) vibration, while at +3.8 G(x), the largest heart rate increase occurred during high-frequency (16 Hz) vibration, demonstrating interaction. DISCUSSION: Consistent with previous reports, our G-loading and vibration effects are similar to mild exercise. In addition, we observed an interaction between G loading and vibration on heart rate, with maximum heart rates occurring at a higher vibration frequency at +3.8 G(x) compared to +1 G(x). The observed interaction demonstrates that G-loading and vibration effects are not independent and can only be properly assessed during combined exposure.

Cardiovascular change during encoding predicts the nonconscious mere exposure effect.

These studies examined memory encoding to determine whether the mere exposure effect could be categorized as a form of conceptual or perceptual implicit priming and, if it was not conceptual or perceptual, whether cardiovascular psychophysiology could reveal its nature. Experiment 1 examined the effects of study phase level of processing on recognition, the mere exposure effect, and word identification implicit priming. Deep relative to shallow processing improved recognition but did not influence the mere exposure effect for nonwords or word identification implicit priming for words. Experiments 2 and 3 examined the effect of study-test changes in font and orientation, respectively, on the mere exposure effect and word identification implicit priming. Different study-test font and orientation reduced word identification implicit priming but had no influence on the mere exposure effect. Experiments 4 and 5 developed and used, respectively, a cardiovascular psychophysiological implicit priming paradigm to examine whether stimulus-specific cardiovascular reactivity at study predicted the mere exposure effect at test. Blood volume pulse change at study was significantly greater for nonwords that were later preferred than for nonwords that were not preferred at test. There was no difference in blood volume pulse change for words at study that were later either identified or not identified at test. Fluency effects, at encoding or retrieval, are an unlikely explanation for these behavioral and cardiovascular findings. The relation of blood volume pulse to affect suggests that an affective process that is not conceptual or perceptual contributes to the mere exposure effect.

256-slice CT coronary angiography: in vivo dosimetry and technique optimization.

PURPOSE: This study was undertaken to compare the different acquisition protocols available in a last-generation multislice computed tomography scanner used for cardiovascular studies, with particular attention to dosimetric aspects. MATERIALS AND METHODS: Our study compared prospective and retrospective electrocardiographic-gating techniques for cardiac imaging. For each patient, we performed in vivo dose measurements, using Gafchromic film. We compared the effective dose values estimated from the experimental measurements and the dose data reported on the CT console. Image quality was also assessed. RESULTS: Prospective acquisition allows for major dose savings compared to retrospective acquisition (mean effective dose, 4.5 mSv with prospective acquisition versus 27.5 mSv with retrospective acquisition). The agreement between the experimental and software-based dose estimates was excellent and showed below 10% of variation of the measured dose. CONCLUSION: In patients with regular rhythm and a heart rate lower than 75 bpm, the prospective acquisition technique ensures adequate diagnostic results and allows for significant patient dose savings.

The value of time-intensity curves obtained after microbubble contrast agent injection to discriminate responders from non-responders to anti-inflammatory medication among patients with Crohn's disease.

OBJECTIVE: To assess the value of time-intensity curves obtained after sulphur hefluoride-filled microbubble contrast agent injection to discriminate responders from non-responders among patients with Crohn's disease (CD). METHODS: Forty-three patients (29 male and 14 female; mean age ± SD, 48.5 ± 17.17 years) with initial diagnosis of active CD were recruited. In each patient, the therapeutic outcome was assessed after 12 weeks from the beginning of pharmacologic treatment. The terminal ileal loop was scanned after sulphur hexafluoride-filled microbubble injection, and the digital cine-clip registered during the first-pass dynamic enhancement was quantified in gray-scale levels. The percentage of maximal enhancement, time to peak enhancement, and area under the time-intensity curve in responders vs. non-responders were compared by Mann-Whitney U non-parametric test. RESULTS: Responders (n = 25 patients) vs. non-responders (n = 18) differed in the area under the time-intensity curve (621.58 ± 374.53 vs. 1,199.64 ± 386.39 P < 0.05), while they did not differ in percentage of maximal enhancement (41.26 ± 15.22 vs. 43.17 ± 4.41, P = 0.25) and time to peak enhancement (11.31 ± 3.06 vs. 10.12 ± 3.47, P = 0.15). CONCLUSIONS: The area under the time-intensity curve obtained after microbubble injection was the only parameter to discriminate responders from non-responders among patients with CD during pharmacologic treatment. KEY POINTS: • Dynamic ultrasound using microbubble contrast agents can help assess inflammatory bowel disease • Time-intensity curves can assess therapeutic outcome in Crohn's disease (CD) • The area under the time-intensity curve differentiates responders from non-responders during pharmacological treatment.

Converging indicators for assessing individual differences in adaptation to extreme environments.

It is well known that microgravity results in various physiological alterations, for example, head-ward fluid shifts which can impede physiological adaptation. Other factors that may affect crew operational efficiency include disruption of sleep-wake cycles, high workload, isolation, confinement, stress, and fatigue. From an operational perspective, it is difficult to predict which individuals will be most or least affected in this unique environment given that most astronauts are first-time flyers. During future lunar and Mars missions space crews will include both men and women of multi-national origins, different professional backgrounds, and various states of physical condition. Therefore, new methods or technologies are needed to monitor and predict astronaut performance and health, and to evaluate the effects of various countermeasures on crew during long-duration missions. Herein we describe the development and validation of a new methodology for assessing the deleterious effects of spaceflight on crew health and performance. We reviewed several studies conducted in both laboratory and operational environments with men and women ranging in age between 18 to 50 yr. The studies included the following: soldiers performing command and control functions during mobile operations in enclosed armored vehicles; subjects participating in laboratory tests of an anti-motion sickness medication; subjects exposed to chronic hypergravity aboard a centrifuge; and subject responses to 36-h of sleep deprivation. Physiological measurements, performance metrics, and subjective self-reports were collected in each study. The results demonstrate that multivariate converging indicators provide a significantly more reliable method for assessing environmental effects on performance and health than any single indicator.

Activation of transcription factor IL-6 (NF-IL-6) and nuclear factor-kappaB (NF-kappaB) by lipid ozonation products is crucial to interleukin-8 gene expression in human airway epithelial cells.

Ozone (O(3)) is a major component of smog and an inhaled toxicant to the lung. O(3) rapidly reacts with the airway epithelial cell membrane phospholipids to generate lipid ozonation products (LOP). 1-Hydroxy-1-hydroperoxynonane (HHP-C9) is an important LOP, produced from the ozonation of 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphatidylcholine. This LOP, at a biologically relevant concentration (100 microM), increases the activity of phospholipase C, nuclear factors-kappaB (NF-kappaB), and interleukin-6 (NF-IL-6) and the expression of the inflammatory gene, interleukin-8 (IL-8) in a cultured human bronchial epithelial cell line (BEAS-2B). The signaling pathways of ozone and its biologically-active products are as yet undefined. In the present study, we report that the HHP LOP, HHP-C9 (100 microM x 4 h), activated the expression of IL-8 (218 +/- 26% increase over control, n = 4, P < 0.01) through an apparent interaction between the two transcription factors, NF-kappaB and NF-IL-6. Transfection studies using luciferase reporter assays demonstrated that HHP-C9 induced a significant increase in NF-kappaB-DNA binding activity (37 +/- 7% increase over control, n = 6, P < 0.05). Inhibition of NF-kappaB showed a statistically significant but modest decrease in IL-8 release, which suggested a role for another transcription factor, NF-IL-6. Exposure of BEAS-2B cells to HHP-C9 induced a significant increase in the DNA binding activity of NF-IL-6 (45 +/- 11% increase over control, n = 6, P < 0.05). The results of the present study indicate that NF-IL-6 interacts with NF-kappaB in regulating the expression of IL-8 in cultured human airway epithelial cells exposed to LOP, the biological products of ozone in the lung.

A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes: results from the National Health and Examination Survey 1999-2002.

OBJECTIVE: Low-level exposure to some persistent organic pollutants (POPs) has recently become a focus because of their possible link with the risk of diabetes. RESEARCH DESIGN AND METHODS: Cross-sectional associations of the serum concentrations of POPs with diabetes prevalence were investigated in 2,016 adult participants in the National Health and Nutrition Examination Survey 1999-2002. Six POPs (2,2',4,4',5,5'-hexachlorobiphenyl, 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin, 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin, oxychlordane, p,p'-dichlorodiphenyltrichloroethane, and trans-nonachlor) were selected, because they were detectable in >or=80% of participants. RESULTS: Compared with subjects with serum concentrations below the limit of detection, after adjustment for age, sex, race and ethnicity, poverty income ratio, BMI, and waist circumference, diabetes prevalence was strongly positively associated with lipid-adjusted serum concentrations of all six POPs. When the participants were classified according to the sum of category numbers of the six POPs, adjusted odds ratios were 1.0, 14.0, 14.7, 38.3, and 37.7 (P for trend < 0.001). The association was consistent in stratified analyses and stronger in younger participants, Mexican Americans, and obese individuals. CONCLUSIONS: There were striking dose-response relations between serum concentrations of six selected POPs and the prevalence of diabetes. The strong graded association could offer a compelling challenge to future epidemiologic and toxicological research.

Systems biology: new approaches to old environmental health problems.

The environment plays a pivotal role as a human health determinant and presence of hazardous pollutants in the environment is often implicated in human disease. That pollutants cause human diseases however is often controversial because data connecting exposure to environmental hazards and human diseases are not well defined, except for some cancers and syndromes such as asthma. Understanding the complex nature of human-environment interactions and the role they play in determining the state of human health is one of the more compelling problems in public health. We are becoming more aware that the reductionist approach promulgated by current methods has not, and will not yield answers to the broad questions of population health risk analysis. If substantive applications of environment-gene interactions are to be made, it is important to move to a systems level approach, to take advantage of epidemiology and molecular genomic advances. Systems biology is the integration of genomics, transcriptomics, proteomics, and metabolomics together with computer technology approaches to elucidate environmentally caused disease in humans. We discuss the applications of environmental systems biology as a route to solution of environmental health problems.

Molecular modeling of manganese regulation of calmodulin-sensitive adenylyl cyclase from mammalian sperm.

The soluble calmodulin-sensitive isoform of adenylyl cyclase isolated from equine sperm is unique because it requires Mn(2+) rather than Mg(2+) for activity. To gain insight into the molecular action of metals on sperm adenylyl cyclase, the kinetics of Mn(2+) and ATP effect was examined. A biphasic response to increases in ATP concentration was observed when metal was held constant. When [Mn(2+)] exceeded [ATP], however, greatly enhanced enzyme activity was observed. The kinetic profiles were consistent with allosteric activation of adenylyl cyclase by Mn(2+). Linear transformation of the data yielded an apparent K(m) for Mn-ATP of 5.8 mM and calculated V(max) of 12 nM cyclic AMP formed/min/mg. Data analysis using calculated equilibrium concentrations of free and complexed reactants provided similar estimates of these kinetic parameters.

Predictors of response to a behavioral treatment in patients with chronic gastric motility disorders.

Chronic gastric motility disorders have proven intractable to most traditional therapies. Twenty-six patients with chronic nausea and vomiting were treated with a behavioral technique, autonomic training (AT) with directed imagery (verbal instructions), to help facilitate physiological control. After treatment, gastrointestinal symptoms decreased by >30% in 58% of the treated patients. We compared those improved patients to the 43% who did not improve significantly. No significant differences existed in baseline symptoms and autonomic measures between both groups. However, baseline measures of gastric emptying and autonomic function predicted treatment outcome. Patients who improved manifested mild to moderate delay in baseline gastric emptying measures. The percent of liquid gastric emptying at 60 mins and the sympathetic adrenergic measure of percent of change in the foot cutaneous blood flow in response to cold stress test predicted improvement in AT outcome, with clinical diagnostic values of 77% and 71%, respectively. We conclude that AT treatment can be efficacious in some patients with impaired gastric emptying and adrenergic dysfunction. More work is warranted to compare biofeedback therapy with gastric motility patients and controls in population-based studies.