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 (UTR) of NTRK2 (TrkB) kinase domain-deficient truncated isoform (TrkB.T1) and BDNF Val66Met SNP with somatic and psychological symptoms and quality of life in a cohort from the United States (U.S.) (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 quality of life. Validation using United Kingdom BioBank (UKBB) data confirmed the association of rs2013566 with increased likelihood of headache. Several SNPs (rs1627784, rs1624327, 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'UTR 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 quality of life. 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 domains, validated by UKBB data. The rs2013566 homozygous recessive genotype correlates with worsened somatic symptoms and reduced quality of life, emphasizing its clinical significance.

Gut microbiome and symptoms in females with irritable bowel syndrome: a cross-sectional analysis.

Irritable bowel syndrome (IBS), a disorder of gut-brain interaction, is associated with abdominal pain and stool frequency/character alterations that are linked to changes in microbiome composition. We tested whether taxa differentially abundant between females with IBS vs healthy control females (HC) are associated with daily gastrointestinal and psychological symptom severity. Participants (age 18-50 year) completed a 3-day food record and collected a stool sample during the follicular phase. They also completed a 28-day diary rating symptom intensity; analysis focused on the three days after the stool sample collection. 16S rRNA gene sequencing was used for bacterial identification. Taxon abundance was compared between IBS and HC using zero-inflated quantile analysis (ZINQ). We found that females with IBS (n = 67) had greater Bacteroides abundance (q = 0.003) and lower odds of Bifidobacterium presence (q = 0.036) compared to HC (n = 46) after adjusting for age, race, body mass index, fibre intake, and hormonal contraception use. Intestimonas, Oscillibacter, and Phascolarctobacterium were more often present and Christensenellaceae R-7 group, Collinsella, Coprococcus 2, Moryella, Prevotella 9, Ruminococcaceae UCG-002, Ruminococcaceae UCG-005, and Ruminococcaceae UCG-014 were less commonly present in IBS compared to HC. Despite multiple taxon differences in IBS vs HC, we found no significant associations between taxon presence or abundance and average daily symptom severity within the IBS group. This may indicate the need to account for interactions between microbiome, dietary intake, metabolites, and host factors.

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. Thus, we investigated the association of 10 single nucleotide polymorphisms (SNPs) in the regulatory 3' untranslated region (UTR) of NTRK2 (TrkB) kinase domain-deficient truncated isoform (TrkB.T1) and the BDNF Val66Met SNP with somatic and psychological symptoms and quality of life in a U.S. cohort (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 quality of life. Validation using U.K. BioBank (UKBB) data confirmed the association of rs2013566 with increased likelihood of headache. Several SNPs (rs1627784, rs1624327, rs1147198) showed significant associations with muscle pain in our U.S. cohort. Notably, these SNPs are predominantly located in H3K4Me1-enriched regions, suggesting their enhancer and/or transcription regulation potential. Together, our findings suggest that genetic variation within the 3'UTR region of the TrkB.T1 isoform may contribute to comorbid conditions in individuals with IBS, resulting in a spectrum of somatic and psychological symptoms that may influence their quality of life. 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.

Stool and urine trefoil factor 3 levels: associations with symptoms, intestinal permeability, and microbial diversity in irritable bowel syndrome.

Previously we showed that urine trefoil factor 3 (TFF3) levels were higher in females with irritable bowel syndrome (IBS) compared to non-IBS females. To assess if TFF3 is associated with symptoms and/or reflect alterations in gastrointestinal permeability and gut microbiota in an IBS population, we correlated stool and urine TFF3 levels with IBS symptoms, intestinal permeability, stool microbial diversity and relative abundance of predominant bacterial families and genera. We also tested the relationship of stool TFF3 to urine TFF3, and compared results based on hormone contraception use. Samples were obtained from 93 females meeting Rome III IBS criteria and completing 4-week symptom diaries. TFF3 levels were measured by ELISA. Permeability was assessed with the urine lactulose/mannitol (L/M) ratio. Stool microbiota was assessed using 16S rRNA. Stool TFF3, but not urine TFF3, was associated positively with diarrhoea and loose stool consistency. Higher stool TFF3 was also associated with lower L/M ratio and microbial diversity. Of the 20 most abundant bacterial families Mogibacteriaceae and Christensenellaceae were inversely related to stool TFF3, with only Christensenellaceae remaining significant after multiple comparison adjustment. There were no significant relationships between stool or urine TFF3 levels and other symptoms, nor between stool and urine levels. In premenopausal females, urine TFF3 levels were higher in those reporting hormone contraception. Collectively these results suggest that higher stool TFF3 levels are associated with IBS symptoms (loose/diarrhoeal stools), lower gut permeability, and altered stool bacteria composition (decreased diversity and decreased Christensenellaceae), which further suggests that TFF3 may be an important marker of host-bacteria interaction.

Relationships of abdominal pain, reports to visceral and temperature pain sensitivity, conditioned pain modulation, and heart rate variability in irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a heterogeneous condition with a number of pathophysiological mechanisms that appear to contribute to symptom chronicity. One of these is altered pain sensitivity. METHODS: Women between ages 18-45 were recruited the community. Of those enrolled, 56 had IBS and 36 were healthy control (HC) women. Participants completed questionnaires, kept a 4-week symptom diary and had a 12-h Holter placed to assess nighttime heart rate variability including high frequency power (HF), low frequency power (LF), and total power (TP). At mid-follicular phase approximately 80% of women completed a thermal pain sensitivity test with conditioned pain modulation and visceral pain sensitivity using a water load symptom provocation (WLSP) test. KEY RESULTS: As expected, daily abdominal pain was significantly higher in the IBS compared to HC group. There were no differences between the bowel pattern subgroups (IBS-diarrhea [IBS-D], IBS-constipation plus mixed [IBS-CM]). Thermal pain sensitivity did not differ between the IBS and the HC groups, but was significantly higher in the IBS-CM group than the IBS-D group. In the WLSP test, the IBS group experienced significantly more symptom distress than HCs and the IBS-CM group was higher than the IBS-D group. Heart rate variability indicators did not differ between the groups or IBS subgroups. Daily abdominal pain was positively correlated with LF and TP in the IBS group. CONCLUSIONS & INFERENCES: Despite similar levels of abdominal pain in IBS, the IBS-CM group demonstrated greater sensitivity to both thermal and visceral testing procedures.

Metabolomics as a tool for discovery of biomarkers of autism spectrum disorder in the blood plasma of children.

BACKGROUND: The diagnosis of autism spectrum disorder (ASD) at the earliest age possible is important for initiating optimally effective intervention. In the United States the average age of diagnosis is 4 years. Identifying metabolic biomarker signatures of ASD from blood samples offers an opportunity for development of diagnostic tests for detection of ASD at an early age. OBJECTIVES: To discover metabolic features present in plasma samples that can discriminate children with ASD from typically developing (TD) children. The ultimate goal is to identify and develop blood-based ASD biomarkers that can be validated in larger clinical trials and deployed to guide individualized therapy and treatment. METHODS: Blood plasma was obtained from children aged 4 to 6, 52 with ASD and 30 age-matched TD children. Samples were analyzed using 5 mass spectrometry-based methods designed to orthogonally measure a broad range of metabolites. Univariate, multivariate and machine learning methods were used to develop models to rank the importance of features that could distinguish ASD from TD. RESULTS: A set of 179 statistically significant features resulting from univariate analysis were used for multivariate modeling. Subsets of these features properly classified the ASD and TD samples in the 61-sample training set with average accuracies of 84% and 86%, and with a maximum accuracy of 81% in an independent 21-sample validation set. CONCLUSIONS: This analysis of blood plasma metabolites resulted in the discovery of biomarkers that may be valuable in the diagnosis of young children with ASD. The results will form the basis for additional discovery and validation research for 1) determining biomarkers to develop diagnostic tests to detect ASD earlier and improve patient outcomes, 2) gaining new insight into the biochemical mechanisms of various subtypes of ASD 3) identifying biomolecular targets for new modes of therapy, and 4) providing the basis for individualized treatment recommendations.

Anticipation of public speaking and sleep and the hypothalamic-pituitary-adrenal axis in women with irritable bowel syndrome.

BACKGROUND: Evidence suggests that subgroups of patients with irritable bowel syndrome (IBS) are hyper-responsive to a variety of laboratory stress conditions. METHODS: This study compared sleep quality and night time plasma adrenocorticotropic hormone (ACTH) and serum cortisol levels in response to anticipation of public speaking between 43 women with IBS and 24 healthy control women. In addition, comparisons were made between subgroups within the IBS sample based on predominant stool patterns, 22 IBS-constipation and 21 IBS-diarrhea. Subjects slept three nights in a sleep laboratory, and on the third night serial blood samples were drawn every 20 min from 08:00 PM until awakening. As the subjects had different sleep onsets, each subject's results were synchronized to the first onset of stage 2 sleep. KEY RESULTS: Compared the healthy control group, women with IBS had significantly worse sleep efficiency, and higher cortisol but not ACTH levels over the night. However, there were no IBS bowel pattern subgroup differences. Among IBS subjects, cortisol levels early in the night were higher than found in our previous study with a similar protocol but without the threat of public speaking. These results suggest that a social stressor, such as public speaking prior to bedtime, increases cortisol but not ACTH levels suggesting HPA dysregulation in women with IBS. CONCLUSIONS & INFERENCES: This response to a social stressor contributes to our understanding of the relationship of stress to symptom expression in IBS.

Lethal arrhythmias in Tbx3-deficient mice reveal extreme dosage sensitivity of cardiac conduction system function and homeostasis.

TBX3 is critical for human development: mutations in TBX3 cause congenital anomalies in patients with ulnar-mammary syndrome. Data from mice and humans suggest multiple roles for Tbx3 in development and function of the cardiac conduction system. The mechanisms underlying the functional development, maturation, and maintenance of the conduction system are not well understood. We tested the requirements for Tbx3 in these processes. We generated a unique series of Tbx3 hypomorphic and conditional mouse mutants with varying levels and locations of Tbx3 activity within the heart, and developed techniques for evaluating in vivo embryonic conduction system function. Disruption of Tbx3 function in different regions of the developing heart causes discrete phenotypes and lethal arrhythmias: sinus pauses and bradycardia indicate sinoatrial node dysfunction, whereas preexcitation and atrioventricular block reveal abnormalities in the atrioventricular junction. Surviving Tbx3 mutants are at increased risk for sudden death. Arrhythmias induced by knockdown of Tbx3 in adults reveal its requirement for conduction system homeostasis. Arrhythmias in Tbx3-deficient embryos are accompanied by disrupted expression of multiple ion channels despite preserved expression of previously described conduction system markers. These findings indicate that Tbx3 is required for the conduction system to establish and maintain its correct molecular identity and functional properties. In conclusion, Tbx3 is required for the functional development, maturation, and homeostasis of the conduction system in a highly dosage-sensitive manner. TBX3 and its regulatory targets merit investigation as candidates for human arrhythmias.

The capsule drug device: novel approach for drug delivery to the eye.

Treatment of age-macular degeneration requires monthly intravitreal injections, which are costly and have serious risks. The objective of this study was to develop a novel intraocular implant for drug delivery. The capsule drug ring is a reservoir inserted in the lens capsule during cataract surgery, refillable and capable of delivering multiple drugs. Avastin was the drug of interest in this study. Prototypes were manufactured using polymethylmethacrylate sheets as the reservoir material, a semi-permeable membrane for controlled delivery and silicone check valves for refilling. The device showed near zero-order release kinetics and Avastin stability was investigated with accelerated temperature studies.

Catecholamine and cortisol levels during sleep in women with irritable bowel syndrome.

Evidence suggests that patients with irritable bowel syndrome (IBS) are hyper-responsive to environmental, physical and visceral stimuli. IBS patients also frequently report poor sleep quality. This study compared serum cortisol and plasma catecholamine levels during sleep between women with IBS (n = 30) and healthy controls (n = 31), and among subgroups within the IBS sample based on predominant stool patterns, IBS-diarrhoea (n = 14), IBS-constipation (n = 7) and IBS-alternators (n = 9). Cortisol was measured from serial blood samples drawn every 20 min, and catecholamines every hour, in a sleep laboratory from 8 pm until awakening. Because of the varied sleep schedules of the individual participants, each subject's hormone series time base was referenced with respect to their onset of Stage 2 sleep. Overall, there were no significant differences in cortisol or catecholamine patterns between women with IBS and controls, nor were there any group by time interactions. However, women with constipation-predominant IBS demonstrated significantly increased noradrenaline, adrenaline and cortisol levels throughout the sleep interval, and women with diarrhoea-predominant IBS were significantly lower on noradrenaline and cortisol. These results suggest that differences in neuroendocrine levels during sleep among IBS predominant bowel pattern subgroups may be greater than differences between IBS women and controls. Neuroendocrine profiles during sleep may contribute to our understanding of symptom expression in IBS.

PAP: a comprehensive workbench for mammalian transcriptional regulatory sequence analysis.

Given the recent explosion of publications that employ microarray technology to monitor genome-wide expression and that correlate these expression changes to biological processes or to disease states, the determination of the transcriptional regulation of these co-expressed genes is the next major step toward deciphering the genetic network governing the pathway or disease under study. Although computational approaches have been proposed for this purpose, there is no integrated and user-friendly software application that allows experimental biologists to tackle this problem in higher eukaryotes. We have previously reported a systematic, statistical model of mammalian transcriptional regulatory sequence analysis. We have now made crucial extensions to this model and have developed a comprehensive, user-friendly web application suite termed the Promoter Analysis Pipeline (PAP). PAP is available at: http://bioinformatics.wustl.edu/webTools/portalModule/PromoterSearch.do.

Heart rate variability is related to pain severity and predominant bowel pattern in women with irritable bowel syndrome.

This study examined heart rate variability (HRV) in women with irritable bowel syndrome (IBS) to determine its association with gut pain and predominant bowel pattern. Women with IBS (constipation predominant n = 45, diarrhoea predominant n = 64, alternating n = 56) and healthy controls (n = 50) were recruited from the community. Severity of gut pain was measured retrospectively. The HRV (24 h) was summarized as high-frequency (HF) power and the ratio of low-frequency (LF) power to HF power. Among those women with IBS who have severe gut pain, the 15 constipation-predominant women had lower (P = 0.01) HF power and higher (P = 0.003) LF/HF ratio (geometric means 70 and 7.5, respectively) than the 21 women with diarrhoea-predominant IBS (286 and 3.1) and controls (224 and 3.9). In contrast, among women without severe pain, there is a smaller and not quite significant difference in the opposite direction. Using a broader definition of pain severity based on several questions nearly doubles the number of subjects in the severe pain group and shows even more significant results. The relationship of predominant bowel pattern to HRV is qualitatively different in the subgroup of patients with more severe pain than in the subgroup with less severe pain.

Subjective and objective sleep indices in women with irritable bowel syndrome.

Patients with irritable bowel syndrome (IBS) commonly report sleep disturbances. This study examined self-report (Pittsburgh Sleep Quality Inventory) sleep quality and polysomnography (PSG) sleep variables in 18 women with mild-to-moderate IBS, 18 with severe IBS and 38 with age- and gender-matched controls. All women were studied on two consecutive nights in a sleep research laboratory where PSG data were collected. Retrospective and daily measures were obtained of self-reported sleep quality, psychological distress and gastrointestinal symptoms across one menstrual cycle. Self-report measures of psychological distress and sleep quality were significantly worse in the IBS-severe (IBS-S) group compared with controls. Rapid eye movement (REM) latency was higher in the two IBS groups on Night 1 than the control group (P = 0.06). Percentage time in REM was highest in the IBS-S on Night 2. All groups demonstrated greater sleep disruption on Night 1 (adaptation) when compared with Night 2. These results highlight the importance of considering the 'first-night effect' in those with IBS and the lack of concordance between self-report and objective indices of sleep in women with IBS.

Relationship of cerebral perfusion pressure levels to outcome in traumatic brain injury.

This study examined the relationship of cumulative percent time that cerebral perfusion pressure (CPP) fell below set thresholds to outcome in individuals with traumatic brain injury (TBI). The sample included 157 patients (16 to 89 years of age, 79%, male) admitted to an intensive care unit at an academic medical center who underwent invasive arterial blood pressure and intracranial pressure monitoring. CPP levels were recorded continuously during the first 96 hours of monitoring. Initial neurologic status was assessed using the post-resuscitation Glasgow Coma Scale. Outcome was evaluated at hospital discharge and at six months post-injury using the Extended Glasgow Outcome Scale (GOSE). The relationship of cumulative periods of low CPP to outcome was evaluated using hierarchical and binary logistic regression analysis, controlling for age, gender, and injury severity. Patients experiencing less cumulative percent time below specific CPP thresholds were more likely to have better outcome at discharge (55 mm Hg, p = .004; 60 mm Hg, p = .008; 65 mm Hg, p = .024; 70 mm Hg, p = .016). Although differences in GOSE scores at six months were not significant, those with less time below CPP thresholds were more likely to survive. Accumulated episodes of low CPP had a stronger negative relationship with outcome in patients with more severe primary brain injury.

Information technology and CPP management in neuro intensive care.

This study developed and tested the acceptability of a computer interface intended to provide better information about CPP to Neuro Intensive Care nurses. Maintaining adequate CPP is crucial in preventing secondary brain injury, yet current monitoring data displays have poor ergonomics that minimize usable information for clinicians. Information systems developmental methods were used to 1) formulate the model for CPP information display, 2) develop the system with end-users, and 3) install the system in the Neuro Intensive Care Unit. System testing for effects on clinicians and patient outcomes is occurring in a randomized clinical trial. Metaphor graphic and universal graphic displays were tested with 37 staff nurses from three intensive care units using continuous ICP monitoring. Nursing staff preferred an augmented universal data display to the metaphor graphics, endorsing a modified trend area graph with threshold-dependent properties. The preferred model was programmed in Visual Basic and installed on small computers that were randomly allocated as live or blank displays to beds of newly admitted head injury or aneurysmal subarachnoid hemorrhage patients with continuous monitoring. Nursing acceptability of the information interface was achieved through the use of end-user focus groups that resulted in modifying the metaphor graphic approach to a more readily understandable one.

A randomised trial of an intervention package designed to promote external cephalic version at term.

OBJECTIVE: To evaluate the effectiveness of an intervention package to promote external cephalic version (ECV). STUDY DESIGN: (1) Design and Setting--A randomised-controlled trial of 20 consultant-based maternity units in the West Midlands NHS Region. (2) Intervention Units--One consultant obstetrician from each unit was encouraged to promote changes in clinical practice within their unit. A multifaceted package including a workshop, written material, guidelines and videos was delivered to these consultants. (3) Control Units--No intervention. (4) Main Outcome Measure--The percentage of women with breech presentation at term who were offered ECV in the antenatal clinic, before and after the intervention. RESULTS: Pre-intervention, there was no difference between the intervention and control units in the proportion of women offered ECV (20 and 19%, respectively). Post-intervention, the proportions were 15% in the control group and 36% in the intervention group (P=0.016). CONCLUSION: This type of intervention package can alter clinical practice and increase the proportion of women with breech presentation at term being offered ECV after the intervention.

Cerebral autoregulation and outcome in acute brain injury.

The purpose of this study was to examine the relationship between Czosnyka and others' Pressure Reactivity Index (PRx) and neurologic outcome in patients with acute brain injury, including traumatic brain injury (TBI) and cerebrovascular pathology. PRx measures the correlation between arterial blood pressure and intracranial pressure waves and may reflect cerebral autoregulation in response to blood pressure changes. A negative PRx reflects intact cerebrovascular response, whereas a positive PRx reflects impaired response. Positive PRx has been shown to correlate with poorer outcome in individuals with TBI, but these findings have not been confirmed by replication in other studies, nor have PRx values been reported for individuals with cerebrovascular pathology. In this study, PRx was determined in 52 patients with TBI (n = 27) or cerebrovascular pathology (n = 25). Hierarchical linear regression was used to evaluate the contribution of PRx to outcome, controlling for age and Glasgow Coma Scale score. Analysis of all subjects together did not support the previously reported relationship between PRx and outcome. However, for those with TBI, positive PRx was a significant predictor of negative outcome (P = 0.03). For those with cerebrovascular pathology, the effect was not significant (P = 0.10) and was in the opposite direction. For individuals with TBI, PRx may provide useful information related to cerebral autoregulation that is predictive of outcome. The meaning of PRx in individuals with cerebrovascular pathology is unclear, and further study is needed to examine the paradoxical findings observed.

Alcohol, aging, and cognitive performance in a cohort of Japanese Americans aged 65 and older: the Kame project.

OBJECTIVE: To investigate the effects of light to moderate alcohol consumption on cognitive performance. DESIGN AND SETTING: A cross-sectional analysis including older Japanese Americans in King County, WA, enrolled in the Kame Project, a population-based study of cognition, dementia, and aging. PARTICIPANTS: 1,836 cognitively intact participants aged 65 and older who participated in the baseline (1992-1994) examination. MEASUREMENT: Cognitive performance was measured using the Cognitive Abilities Screening Instrument, reaction time (simple and choice), and a measure of vocabulary (North American Adult Reading Test). RESULTS: Multivariate analyses were used to examine the relationship between cognitive performance and alcohol consumption at baseline with men and women together and then separately controlling for age, education, smoking, history of stroke, angina, hypertension, diabetes, and coronary heart disease. Findings showed lower cognitive test scores were observed for men who were either abstainers or in the heavy drinking group. For women, a linear relationship between alcohol consumption and cognitive performance was seen on two of the four measures of cognitive functioning. No significant difference in the association of drinking and cognitive function was identified within the different Japanese American subgroups. CONCLUSION: RESULTS suggest a possible positive relationship between light to moderate drinking and cognitive performance in an aging Japanese American population. Additional long-term prospective and cross-cultural studies are needed to determine the generalizability of these findings to other aging cohorts.

A decision analytical cost analysis of offering ECV in a UK district general hospital.

OBJECTIVE: To determine the care pathways and implications of offering mothers the choice of external cephalic version (ECV) at term for singleton babies who present with an uncomplicated breech pregnancy versus assisted breech delivery or elective caesarean. DESIGN: A prospective observational audit to construct a decision analysis of uncomplicated full term breech presentations. SETTING: The North Staffordshire NHS Trust. SUBJECTS: All women (n = 176) who presented at full term with a breech baby without complications during July 1995 and June 1997. MAIN OUTCOME MEASURES: The study determined to compare the outcome in terms of the costs and cost consequences for the care pathways that resulted from whether a women chose to accept the offer of ECV or not. All the associated events were then mapped for the two possible pathways. The costs were considered only within the hospital setting, from the perspective of the health care provider up to the point of delivery. RESULTS: The additional costs for ECV, assisted breech delivery and elective caesarean over and above a normal birth were 186.70 pounds sterling, 425.36 pounds sterling and 1,955.22 pounds sterling respectively. The total expected cost of the respective care pathways for "ECV accepted" and "ECV not accepted" (including the probability of adverse events) were 1,452 pounds sterling and 1,828 pounds sterling respectively, that is the cost of delivery through the ECV care pathways is less costly than the non ECV delivery care pathway. CONCLUSIONS: Implementing an ECV service may yield cost savings in secondary care over and above the traditional delivery methods for breech birth of assisted delivery or caesarean section. The scale of these expected cost savings are in the range of 248 pounds sterling to 376 pounds sterling per patient. This converts to a total expected cost saving of between 43,616 pounds sterling and 44,544 pounds sterling for the patient cohort considered in this study.

Autonomic nervous system function in women with irritable bowel syndrome.

Autonomic nervous system (ANS) balance was assessed in women with and without irritable bowel syndrome (IBS) using laboratory tests of function (ie, expiratory/inspiratory ratio, Valsalva, posture changes, and cold pressor) and spectral and nonspectral measures of heart rate variability (HRV). Women with (N = 103) and without IBS (N = 49) were recruited, interviewed, then completed a laboratory assessment and wore a 24-hr Holter monitor Analysis using the entire sample showed little difference between IBS and control women and between subgroups with IBS on either laboratory measures or 24-hr HRV measures. However, analysis restricted to those women with severe IBS symptoms showed quite pronounced differences between two IBS subgroups on 24-hr HRV measures. Parasympathetic tone was significantly lower and ANS balance was significantly higher in the constipation-predominant compared to the diarrhea-predominant group. Subgroups of women with IBS do differ in ANS function as measured by 24-hr HRV; however, these differences are only apparent among women with severe symptoms. These findings point out the importance of considering symptom severity when interpreting studies of IBS.