Age Differences in Core Symptoms and Symptom Relationships in Patients With Irritable Bowel Syndrome: A Network Analysis.

INTRODUCTION: Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction, characterized by symptoms of abdominal pain and changes in bowel habits. It often co-occurs with extraintestinal somatic and psychological symptoms. However, the nature of the interrelationships among these symptoms is unclear. Although previous studies have noted age differences in IBS prevalence and specific symptom severity, it remains unknown whether specific symptoms and symptom relationships may differ by age. METHODS: Symptom data were collected in 355 adults with IBS (mean age 41.4 years, 86.2% female). Network analysis was used to examine the interrelationships among 28 symptoms and to identify the core symptoms driving the symptom structure between young (≤45 years) vs older (>45 years) adults with IBS. We evaluated 3 network properties between the 2 age groups: network structure, edge (connection) strength, and global strength. RESULTS: In both age groups, fatigue was the top core symptom. Anxiety was a second core symptom in the younger age group, but not the older age group. Intestinal gas and/or bloating symptoms also exerted considerable influences in both age groups. The overall symptom structure and connectivity were found to be similar regardless of age. DISCUSSION: Network analysis suggests fatigue is a critical target for symptom management in adults with IBS, regardless of age. Comorbid anxiety is likely an important treatment focus for young adults with IBS. Rome V criteria update could consider the importance of intestinal gas and bloating symptoms. Additional replication with larger diverse IBS cohorts is warranted to verify our results.

Physical function, psychological adjustment, and self-efficacy following sudden cardiac arrest and an initial implantable cardioverter defibrillator (ICD) in a social cognitive theory intervention: secondary analysis of a randomized control trial.

BACKGROUND: Sudden cardiac arrest (SCA) survivorship results in unique issues in return to physical and psychological function. The purpose of the study was to compare recovery across the first year between SCA survivors and other arrhythmia patients who received a first-time implantable cardioverter defibrillator (ICD) for secondary prevention, participating in a social cognitive theory (SCT) intervention. METHODS: 168 (129 males, 39 females) who received an ICD for secondary prevention (SCA N = 65; other arrhythmia N = 103) were randomized to one of two study conditions: SCT intervention (N = 85) or usual care (N = 83). Outcomes were measured at baseline hospital discharge, 1, 3, 6, & 12 months: (1) Physical Function: Patient Concerns Assessment (PCA), SF-36 (PCS); (2) Psychological Adjustment: State Trait Anxiety (STAI), CES-D depression, SF-36 (MCS); (3) Self-Efficacy: Self-Efficacy (SCA-SE), Self-management Behaviors (SMB), Outcome Expectations (OE). Outcomes were compared over 12 months for intervention condition x ICD indication using general estimating equations. RESULTS: Participants were Caucasian (89%), mean age 63.95 ± 12.3 years, EF% 33.95 ± 13.9, BMI 28.19 ± 6.2, and Charlson Index 4.27 ± 2.3. Physical symptoms (PCA) were higher over time for SCA survivors compared to the other arrhythmia group (p = 0.04), ICD shocks were lower in SCA survivors in the SCT intervention (p = 0.01); psychological adjustment (MCS) was significantly lower in SCA survivors in the SCT intervention over 6 months, which improved at 12 months (p = 0.05); outcome expectations (OE) were significantly lower for SCA survivors in the SCT intervention (p = 0.008). CONCLUSIONS: SCA survivors had greater number of physical symptoms, lower levels of mental health and outcome expectations over 12 months despite participation in a SCT intervention. Trial registration Clinicaltrials.gov: NCT04462887.

Relationships of Microbiome Markers With Extraintestinal, Psychological Distress and Gastrointestinal Symptoms, and Quality of Life in Women With Irritable Bowel Syndrome.

INTRODUCTION: Altered microbial diversity has been associated with gastrointestinal (GI) symptoms in persons with irritable bowel syndrome (IBS). Less is known about the relationship of microbiome with extraintestinal pain and psychological distress symptoms and quality of life (QOL) in persons with IBS. We aimed to evaluate the relationship of fecal microbiota to GI symptoms, stool consistency, psychological distress, extraintestinal pain, and QOL in participants meeting Rome III criteria for IBS. METHODS: Seventy-six women completed a 28-day diary that included GI, stool consistency, psychological distress, and extraintestinal pain ratings. Participants completed the IBS-Specific Quality of Life questionnaire. Stool samples were collected and analyzed by 16S rRNA gene sequencing. Principal component analysis was performed and the first 2 components (PC1, PC2) were used to test relationships among bacterial families and clinical measures. RESULTS: Participants were categorized as IBS constipation (n=22), IBS diarrhea (n=39), IBS mixed (n=13), and IBS unsubtyped (n=2). There was a significant group effect for the Firmicutes to Bacteroidetes ratio and PC1. Lower microbial diversity and richness were associated with increased urgency and extraintestinal pain, worse QOL, and looser stools. Lower extraintestinal pain was associated with increased Rikenellaceae, Christensenellaceae, Dehalobabacteriaceae, Oscillospiraceae, Mogibacteriaceae, Ruminococcaceae, Sutterellaceae, Desulfovibrionaceae, and Erysipelotrichaceae abundances. QOL was positively associated with many of these same bacterial families. Higher Firmicutes to Bacteroidetes ratio was positively associated with loose stools. There were no statistically significant relationships between daily psychological distress or abdominal pain and bacterial families. CONCLUSIONS: Stool microbial diversity and composition are linked to daily extraintestinal symptoms, stool consistency, and QOL in women with IBS.

During stress, heart rate variability moderates the impact of childhood adversity in women with breast cancer.

Childhood adversity has long-lasting neuro-biological effects that can manifest as exaggerated stress responsivity to environmental challenge. These manifestations include a dysregulated hypothalamic-pituitary-adrenocortical (HPA) axis as well as increased levels of inflammatory mediators in response to stress. In this investigation, vagal parasympathetic activity was assessed for its capacity to moderate the relationship between childhood adversity and stress responsivity (cortisol and inflammation) during an acute laboratory challenge (Trier Social Stress Test-TSST). Thirty women recently diagnosed with breast cancer underwent the TSST during which their heart rate was recorded and saliva samples collected for measurement of cortisol and the proinflammatory cytokine, IL-6. Vagal activity during the TSST was calculated as the high-frequency (HF) component of heart rate variability (HRV). Vagal activity during the TSST moderated the effect of childhood adversity on both the cortisol and the IL-6 response. Women who had lower vagal stress-reactivity during the TSST and reported greater childhood adversity showed a larger rise in cortisol and IL-6 when compared to women with lower childhood adversity. The findings demonstrate that women with exposure to childhood adversity and low vagal stress-reactivity (reduced parasympathetic activity) exhibit an elevated stress response characterized by greater cortisol and proinflammatory cytokine release. Inflammatory burden and HPA dysregulation subsequent to stress may impair cancer control.

Prospective randomized trial of moderately strenuous aerobic exercise after an implantable cardioverter defibrillator.

BACKGROUND: Despite its salutary effects on health, aerobic exercise is often avoided after receipt of an implantable cardioverter defibrillator (ICD) because of fears that exercise may provoke acute arrhythmias. We prospectively evaluated the effects of a home aerobic exercise training and maintenance program (EX) on aerobic performance, ICD shocks, and hospitalizations exclusively in ICD recipients. METHODS AND RESULTS: A total of 160 patients (124 men and 36 women) were randomly assigned who had an ICD for primary (43%) or secondary (57%) prevention to EX or usual care (UC). The primary outcome was peak oxygen consumption, measured with cardiopulmonary exercise testing at baseline and 8 and 24 weeks. EX consisted of 8 weeks of home walking for 1 h/d, 5 d/wk at 60% to 80% of heart rate reserve, followed by 16 weeks of maintenance home walking for 150 min/wk. Adherence to EX was determined from exercise logs, ambulatory heart rate recordings of exercise, and weekly telephone contacts. Patients assigned to UC received no exercise directives and were monitored by monthly telephone contact. Adverse events were identified by ICD interrogations, patient reports, and medical charts. ICD recipients averaged 55±12 years and mean ejection fraction of 40.6±15.7; all were taking ß-blocker medications. EX significantly increased peak oxygen consumption (EX, 26.7±7.0 mL/kg per minute; UC, 23.9±6.6 mL/kg per minute; P=0.002) at 8 weeks, which persisted during maintenance exercise at 24 weeks (EX, 26.9±7.7 mL/kg per minute; UC, 23.4±6.0 mL/kg per minute; P<0.001). ICD shocks were infrequent (EX=4 versus UC=8), with no differences in hospitalizations or deaths between groups. CONCLUSIONS: Prescribed home exercise is safe and significantly improves cardiovascular performance in ICD recipients without causing shocks or hospitalizations. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00522340.

Adherence to an Aerobic Exercise Intervention after an Implantable Cardioverter Defibrillator (ICD).

BACKGROUND: Exercise adherence is an important element in achieving important exercise outcomes. The purpose of this study was to describe adherence in a home-based aerobic exercise program following an implantable cardioverter defibrillator (ICD), determine effects of adherence on peakVO2 , and outline reasons for nonadherence. METHODS AND RESULTS: A single-blind randomized control trial of home walking compared to usual care in 160 patients with an ICD for primary or secondary prevention was conducted. This report is on adherence in the exercise arm (N = 84). Home walking exercise consisted of 8 weeks of aerobic conditioning (60 minutes/day, 5 days/week) followed by 16 weeks of aerobic maintenance (150 minutes/week, 30 minutes/session) at 60-80% of heart rate reserve. Adherence was tracked using Polar heart rate (HR) monitors, pedometers, home exercise logs, and telephone follow-up. Adherence was defined as performing at least 80% of prescribed exercise. For aerobic conditioning, there was a mean frequency of 3.81 walks/week, duration of 1,873 minutes walked, and 17.5% of exercise was in the target HR (THR) zone. For aerobic maintenance, there was a mean frequency of 2.4 walks/week, duration of 1,872 minutes/walked, and 8.7% of exercise was in the THR zone. Those who were 80% adherent achieved a 3.4 mL/kg/min (P = 0.03) improvement in peakVO2 over those who were <80% adherent. Reasons for nonadherence to exercise ranged from scheduling issues to viral illness and fatigue. CONCLUSIONS: Adherence to aerobic exercise frequency and duration was high with few dropouts, resulting in higher peakVO2 . Exercise monitoring equipment encouraged adherence and conferred a sense of safety to exercise.

Safety and Efficacy of an Early Home-Based Walking Program After Receipt of an Initial Implantable Cardioverter-Defibrillator.

OBJECTIVE: To assess the safety and efficacy of an early home-based walking program for first-time implantable cardioverter-defibrillator (ICD) recipients. DESIGN: Pre-post intervention trial. SETTING: Institutional and private practice. PARTICIPANTS: Cardiac patients (N=301) with an initial ICD implantation for primary or secondary prevention; able to read, speak, and write English; and having access to telephone. INTERVENTIONS: Early home-based walking protocol implemented 1-month post-ICD implant. Exercise tolerance monitored by study nurses via telephone. MAIN OUTCOME MEASURES: Safety assessment was based on the frequency of ICD therapies and hospitalizations, and efficacy assessment was based on pedometer measures and self-report of ICD self-efficacy and physical activity. RESULTS: ICD recipients were on average 64.1±11.9 years old, predominantly men, and white, with an ejection fraction of <35% and a mean Charlson comorbidity score of 2.3±1.5. Nineteen individuals (6.3%) received 28 ICD shocks; 15 (53.6%) were appropriate and 13 (46.4%) inappropriate. Antitachycardia pacing therapies were delivered 72 times in 18 individuals (6%), with 61 (84.7%) being appropriate and 11 (15.3%) inappropriate. Five ICD shocks (2 appropriate and 3 inappropriate) and 2 antitachycardia pacing therapies occurred during walking. Five participants (2%) were hospitalized for an ICD shock, none of which was associated with walking. Average steps per day increased by 806 over 3 months. Perceived exercise self-efficacy improved significantly as did weekly exercise. Predictors of receiving any ICD shock were younger age (P<.0001), moderate to severe renal disease (P=.001), and lymphoma (P=.024). CONCLUSIONS: Early ambulation after an initial ICD was safe and effective, with few ICD shocks and improved efficacy.

Anxiety, depression, and catecholamine levels after self-management intervention in irritable bowel syndrome.

Patients with irritable bowel syndrome (IBS) often report higher levels of psychological distress, specifically anxiety, and depression than non-IBS patients. The management of gastrointestinal symptoms and psychological distress is demonstrably amenable to cognitive-behavioral therapies in a significant number of patients with IBS. The present secondary analysis evaluates the impact of nurse-delivered self-management interventions on anxiety, depression, and urine catecholamine levels in adult IBS patients. Participants in the study were randomized to 2 intervention groups of either comprehensive self-management (CSM) intervention or usual care control. Daily diary ratings of gastrointestinal symptoms, anxiety, and depression were recorded every evening for 28 days during the baseline period and subsequently at 3, 6, and 12 months postrandomization. Catecholamine levels of epinephrine and norepinephrine were measured from 4 weekly 1st morning urine samples at baseline as well as at each follow-up time. The CSM group reported significantly lower levels of anxiety and depression at follow-up than the usual care group (p = .018 and .021, respectively). In contrast, urine catecholamine levels displayed no appreciable change. Thus, although nurse-delivered CSM interventions showed no impact on urinary catecholamine levels, daily psychological distress was measurably reduced.

Aerobic Exercise Improves Heart Rate Variability After an Implantable Cardioverter Defibrillator (ICD).

CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT00522340.

Genetic Variations in TrkB.T1 Isoform and Their Association With Somatic and Psychological Symptoms in Individuals With IBS.

Irritable bowel syndrome (IBS), a disorder of gut-brain interaction, is often comorbid with somatic pain and psychological disorders. Dysregulated signaling of brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), has been implicated in somatic-psychological symptoms in individuals with IBS. We investigated the association of 10 single-nucleotide polymorphisms (SNPs) in the regulatory 3' untranslated region of neurotrophic receptor tyrosine kinase-2 (NTRK2) kinase domain-deficient truncated isoform (TrkB.T1) and BDNF Val66Met SNP with somatic and psychological symptoms and quality-of-life (QoL) in a cohort from the United States (IBS, n = 464; healthy controls, n = 156). We found that the homozygous recessive genotype (G/G) of rs2013566 in individuals with IBS is associated with worsened somatic symptoms, including headache, back pain, joint pain, muscle pain, and somatization as well as diminished sleep quality, energy level, and overall QoL. Validation using United Kingdom BioBank data confirmed the association of rs2013566 with an increased likelihood of headache. Several SNPs (rs1627784, rs1624327, and rs1147198) showed significant associations with muscle pain in our U.S. cohort. These 4 SNPs are predominantly located in H3K4Me1-enriched regions, suggesting their enhancer and/or transcription regulation potential. Our findings suggest that genetic variation within the 3' untranslated region region of the TrkB.T1 isoform may contribute to comorbid conditions in individuals with IBS, resulting in a spectrum of somatic and psychological symptoms impacting their QoL. These findings advance our understanding of the genetic interaction between BDNF/TrkB pathways and somatic-psychological symptoms in IBS, highlighting the importance of further exploring this interaction for potential clinical applications. PERSPECTIVE: This study aims to understand the genetic effects on IBS-related symptoms across somatic, psychological, and quality-of-life (QoL) domains, validated by United Kingdom BioBank data. The rs2013566 homozygous recessive genotype correlates with worsened somatic symptoms and reduced QoL, emphasizing its clinical significance.

Rest-Activity Rhythm Fragmentation and Weaker Circadian Strength Are Associated With Cognitive Impairment in Survivors of Acute Respiratory Failure.

Background: Survivors of acute respiratory failure (ARF) experience long-term cognitive impairment and circadian rhythm disturbance after hospital discharge. Although prior studies in aging and neurodegenerative diseases indicate actigraphy-estimated rest-activity circadian rhythm disturbances are risk factors for cognitive impairment, it is unclear if this applies to ARF survivors. This study explored the relationships of actigraphy-estimated rest-activity circadian rhythms with cognitive functioning in ARF survivors at 3 months after discharge. Methods: 13 ARF survivors (mean age 51 years and 69% males) completed actigraphy and sleep diaries for 9 days, followed by at-home neuropsychological assessment. Principal component factor analysis created global cognition and circadian rhythm variables, and these first components were used to examine the global relationships between circadian rhythm and cognitive measure scores. Results: Global circadian function was associated with global cognition function in ARF survivors (r = .70, p = .024) after adjusting for age, education, and premorbid cognition. Also, greater fragmented rest-activity circadian rhythm (estimated by intradaily variability, r = .85, p = .002), and weaker circadian strength (estimated by amplitude, r = .66, p = .039; relative strength, r = .70, p = .024; 24-h lag serial autocorrelation, r = .67, p = .035), were associated with global cognition and individual cognitive tests. Conclusions: These results suggest circadian rhythm disturbance is associated with poorer global cognition in ARF survivors. Future prospective research with larger samples is needed to confirm these results and increase understanding of the relationship between disrupted circadian rhythms and cognitive impairment among ARF survivors.

Exploration of associations among dietary tryptophan, microbiome composition and function, and symptom severity in irritable bowel syndrome.

BACKGROUND: Imbalance of the tryptophan (TRP) pathway may influence symptoms among patients with irritable bowel syndrome (IBS). This study explored relationships among different components that contribute to TRP metabolism (dietary intake, stool metabolite levels, predicted microbiome metabolic capability) in females with IBS and healthy controls (HCs). Within the IBS group, we also investigated relationships between TRP metabolic determinants, Bifidobacterium abundance, and symptoms of IBS. METHODS: Participants with IBS (Rome III) and HCs completed a 28-day diary of gastrointestinal symptoms and a 3-day food record for TRP intake. They provided a stool sample for shotgun metagenomics, 16 S rRNA analyses, and quantitative measurement of TRP by mass spectrometry. RESULTS: Our cohort included 115 females, 69 with IBS and 46 HCs, with a mean age of 28.5 years (SD 7.4). TRP intake (p = 0.71) and stool TRP level (p = 0.27) did not differ between IBS and HC. Bifidobacterium abundance was lower in the IBS group than in HCs (p = 0.004). Predicted TRP metabolism gene content was higher in IBS than HCs (FDR-corrected q = 0.006), whereas predicted biosynthesis gene content was lower (q = 0.045). Within the IBS group, there was no association between symptom severity and TRP intake or stool TRP, but there was a significant interaction between Bifidobacterium abundance and TRP intake (q = 0.029) in predicting stool character. CONCLUSIONS: Dietary TRP intake, microbiome composition, and differences in TRP metabolism constitute a complex interplay of factors that could modulate IBS symptom severity.

Physical activity patterns of patients with cardiopulmonary illnesses.

OBJECTIVES: The aims of this paper were (1) to describe objectively confirmed physical activity patterns across 3 chronic cardiopulmonary conditions, and (2) to examine the relationship between selected physical activity dimensions with disease severity, self-reported physical and emotional functioning, and exercise performance. DESIGN: Cross-sectional study. SETTING: Participants' home environment. PARTICIPANTS: Patients with cardiopulmonary illnesses: chronic obstructive pulmonary disease (COPD) (n=63), heart failure (n=60), and patients with implantable cardioverter defibrillator (n=60). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Seven ambulatory physical activity dimensions (total steps, percent time active, percent time ambulating at low, medium, and high intensity, maximum cadence for 30 continuous minutes, and peak performance) were measured with an accelerometer. RESULTS: Subjects with COPD had the lowest amount of ambulatory physical activity compared with subjects with heart failure and cardiac dysrhythmias (all 7 activity dimensions, P<.05); total step counts were: 5319 versus 7464 versus 9570, respectively. Six-minute walk distance was correlated (r=.44-.65, P<.01) with all physical activity dimensions in the COPD sample, the strongest correlations being with total steps and peak performance. In subjects with cardiac impairment, maximal oxygen consumption had only small to moderate correlations with 5 of the physical activity dimensions (r=.22-.40, P<.05). In contrast, correlations between 6-minute walk test distance and physical activity were higher (r=.48-.61, P<.01) albeit in a smaller sample of only patients with heart failure. For all 3 samples, self-reported physical and mental health functioning, age, body mass index, airflow obstruction, and ejection fraction had either relatively small or nonsignificant correlations with physical activity. CONCLUSIONS: All 7 dimensions of ambulatory physical activity discriminated between subjects with COPD, heart failure, and cardiac dysrhythmias. Depending on the research or clinical goal, use of 1 dimension, such as total steps, may be sufficient. Although physical activity had high correlations with performance on a 6-minute walk test relative to other variables, accelerometry-based physical activity monitoring provides unique, important information about real-world behavior in patients with cardiopulmonary illness not already captured with existing measures.

Cognitive Behavioral Therapy-Based Comprehensive Self-Management Program Improves Presenteeism in Persons with Irritable Bowel Syndrome: A Secondary Data Analysis.

Individuals with irritable bowel syndrome (IBS) are more likely to miss work (absenteeism), have reduced work effectiveness (presenteeism) and experience activity impairment. This study compared the effect of a comprehensive self-management (CSM) intervention program (incorporating cognitive behavioral therapy, diet education and relaxation) versus usual care on work- and activity-impairments in adults with IBS. This secondary data analysis used daily diaries and Work Productivity and Activity Impairment in Irritable Bowel Syndrome (WPAI-IBS) questionnaire data collected at baseline, 3, 6 and 12 months post-randomization from 160 adults with IBS. Mixed-effects modeling was used to compare the effect of CSM versus usual care on work- and activity-related outcomes. The effect of CSM was shown to be superior to usual care in improving WPAI-IBS and diary-measured presenteeism, overall work productivity loss and activity impairment with sustained effects up to 12 months post-randomization (all p < 0.05). Moreover, the CSM intervention was found to be particularly beneficial for IBS patients with greater baseline work and activity impairments (all p < 0.05). The CSM intervention may bring benefits to individuals and society through improving symptoms and reducing presenteeism associated with IBS.

Does a self-management program change dietary intake in adults with irritable bowel syndrome?

Making dietary changes such as increasing fiber intake is recommended for the management of irritable bowel syndrome symptoms. Few studies have explored the efficacy of education on compliance with recommendations such as increasing fiber, vegetable, and fruit intake in adults with irritable bowel syndrome. This study examined the effect of a multicomponent self-management intervention that included strategies to enhance fiber, vegetable, and fruit intake. Participants with medically diagnosed irritable bowel syndrome were randomized to usual care or individualized comprehensive self-management, delivered either in-person or by telephone. Since previously published analyses show the two delivery modes to be equally effective, the two intervention groups were combined. Of the 188 individuals randomized, 173 participants (113 in the self-management group and 60 in the usual care group; 23 men, 150 women) provided data on at least one of the three follow-up occasions (3, 6, and 12 months postrandomization). Fiber, vegetable, and fruit intakes were measured using the Food Frequency Questionnaire. Participants in the intervention group demonstrated increases (p < .05) in fiber and fruit intake and a trend in vegetable intake at 6 and 12 months postintervention. Improvement in dietary fiber intake following a self-management intervention for IBS continues to 1 year.

Validation of the StepWatch device for measurement of free-living ambulatory activity in patients with chronic obstructive pulmonary disease.

This study examined the validity of the StepWatch activity monitor and the optimal number of monitoring days in patients with chronic obstructive pulmonary disease (COPD). StepWatch activity data were obtained from databases of two studies: one of patients with COPD who participated in a trial of two exercise persistence interventions (n = 17) and a second, cross-sectional study of activity in chronically healthy older adults (n = 60). Independent t tests, Pearson's correlations, and Bland-Altman plots were used to examine the activity data (total steps, activity intensity, and distribution of activity). Results indicated that patients with COPD registered 50% fewer total steps and had lower levels of walking intensity compared with chronically healthy older adults. Activity parameters had moderate-to-high correlations with disease severity, peak cycle workload, and physical functioning. More monitoring days were associated with greater measurement precision. This study provides preliminary evidence to support the validity of the StepWatch device for measuring free-living ambulatory physical activity in COPD.

Heart Rate Variability and Inflammatory Stress Response in Young African American Men: Implications for Cardiovascular Risk.

Background: African American men have a disproportionately higher incidence of and suffer greater severity and earlier death from cardiovascular disease (CVD). A common feature of many diseases, which disproportionately afflict disadvantaged African Americans, is inflammation. In particular, inflammation plays a decisive role in the pathogenesis of CVD in that persistent inflammation contributes to plaque evolution and destabilization. Adverse childhood experiences increase the risk for adult inflammatory based disease, particularly cardiovascular disease. This inflammatory burden becomes evident during stressful events and may be related to alterations in autonomic nervous system (ANS) activity. We previously reported that African American men who experienced childhood adversity exhibited a greater inflammatory (IL-6) response to acute stress challenge (Trier Social Stress Test - TSST). The purpose of this study was to determine whether altered ANS activity, as measured by heart rate variability (HRV), contributes to a greater proinflammatory response to stress in those exposed to childhood adversity. Methods: Thirty-four African American adult males underwent the TSST while instrumented with Holter monitors to record continuous heart rate for HRV determination. HRV was calculated as the low frequency (LF) to high frequency (HF) heart rate ratio (LF/HF), with higher LF/HF ratios corresponding to higher sympathetic vs. parasympathetic activity. Salivary samples were collected pre- and post-TSST to measure the proinflammatory cytokine IL-6. Childhood adversity was assessed by the Childhood Trauma Questionnaire. Results: Hierarchical linear modeling demonstrated that higher levels of physical abuse were related to a steeper rise in LF/HF ratio during the TSST. Further, a higher LF/HF ratio, in combination with greater exposure to emotional and physical abuse was associated with a greater IL-6 response to the TSST. Conclusions: These findings suggest that adverse childhood experiences associate with an adult phenotype characterized by an altered ANS response to stress as well as a greater proinflammatory (IL-6) response to an acute stressor. Elevations in salivary inflammatory markers have been associated with increased CVD risk. In conclusion, these findings suggest a role for the ANS in the underlying neuro-biological processes whereby childhood adversity predisposes to a more intense inflammatory response to stressful challenge during adulthood.

Bile Acids and Microbiome Among Individuals With Irritable Bowel Syndrome and Healthy Volunteers.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. High bile acid (BA) profiles have been associated with abdominal pain symptoms, mucosal inflammation, and diarrhea in a subgroup of those with IBS. The purpose of this study was to compare: 1) fecal primary and secondary BAs in women with and without IBS; and 2) symptoms, gut microbiome, and diet between women with high and normal BAs (i.e., similar to healthy [HC] women). Women (ages 18-45) with IBS and HCs were recruited from healthcare providers or the community. Participants kept a 28-day symptom diary, completed a 3-day food journal, and collected a stool sample for microbiome analysis (16 S rRNA gene sequencing). Primary and secondary BA levels were determined by mass spectrometry. Primary BAs did not differ between IBS (n = 45) and HC (n = 28) groups; women with IBS had significantly increased conjugated secondary BAs (glycodeoxycholic acid [p = 0.006], taurodeoxycholic acid [p = 0.006], and glycolithocholic acid [p = 0.01]). Sixty percent of women with IBS had normal BAs whereas 40% had high BAs. Women with high fecal BAs were predominantly IBS-Diarrhea or IBS-Mixed and consumed less fiber and vegetable protein and more animal protein compared to women with IBS whose fecal BAs levels were comparable to HCs. Those with high conjugated secondary fecal BAs also had a greater Firmicutes/Bacteroidetes ratio, less abundance of phylum Bacteroidetes and genus Gemmiger, and more abundance of family Erysipelotrichaceae compared to IBS women with normal BAs. Determination of fecal BA levels provides additional insights into pathophysiological links between diet and microbiome in IBS.

Associations between chronotype, social jetlag, and weekday sleep in women with irritable bowel syndrome.

Sleep deficiency is well-documented in individuals with irritable bowel syndrome (IBS). Sleep deficiency includes poor sleep quality and an inadequate amount of sleep, and is a modifiable risk factor for IBS symptom exacerbations. Prior studies in other populations have identified chronotype and social jetlag (SJL) as important determinants of sleep outcomes. However, chronotype and SJL have not been examined in women with IBS. We used multiple linear regression analyses to determine whether chronotype and SJL are associated with sleep outcomes during weekdays among women with IBS predominant constipation (IBS-C), IBS with predominant diarrhea (IBS-D), and healthy control (HC) women. This sample included 62 women with IBS (IBS-C = 29, IBS-D = 33) and 58 HC women who completed a 28-day daily diary from two study cohorts. The average age of the participants was 30.1 (SD 7.2) years. Chronotype was estimated from daily diary data with the average mid-sleep time on weekends (MSWwe). SJL was calculated by subtracting the average mid-sleep time on weekdays from MSWwe. Sleep outcomes included diary assessments of sleep quality, sleep need met, and restorative sleep during weekdays. In HCs, later chronotype was predictive of lower sleep quality (ß = -0.19, p < .01), a perception of sleep need not met (ß = -0.17, p < .001), and a less restorative sleep during weekdays (ß = -0.15, p = .073), whereas SJL was not associated with sleep outcomes. Similar to HCs, earlier chronotypes in women with IBS-C reported better sleep quality and more sufficient sleep need met and restorative sleep during weekdays than later chronotypes (all p > .05). Compared to HCs, the relationships of chronotype with weekday sleep outcomes in the women with IBS-D were in the opposite directions (all p < .05). This exploratory study suggests that chronotype expression may reflect the temporal associations of sleep outcomes within IBS bowel pattern predominance subgroups, particularly sleep quality and sleep need met. Additional investigations are warranted to examine whether specific temporal attributes of symptoms and/or symptom severity associated with IBS subgroups contribute to chronotype expression.