A multifaceted ecological approach to explore links between environmental factors and the epidemiology of disorders of gut-brain interaction.

BACKGROUND: Disorders of gut-brain interaction (DGBI) are characterized by debilitating symptoms not explained by structural or biochemical abnormalities. While functional conditions present with complex, likely heterogeneous pathophysiology, we aimed to investigate if proxy measures of sociocultural and environmental factors are associated with the prevalence of various DGBI in populations across the world. METHODS: We performed an ecological study utilizing peer-reviewed published datasets reporting for 26 countries prevalence rates of DGBI (Rome Foundation Global Epidemiology Study, RFGES), with six independent variables: Helicobacter pylori prevalence and household size as proxy measures for orofecal infections, gross domestic product per capita (GDP), and median age as a proxy measures for socioeconomic development, density of fast food outlets (FFO) per 100,000 population as proxy measure for processed food exposure, and suicide mortality rate per 100,000 people, and world happiness scores were used as a proxy for psychological stress. The data were retrieved from publicly accessible datasets (United Nations, CIA World Factbook, World Bank, World Happiness Report, commercial/financial reports of a global FFO chain). We used linear regression to assess variables in univariate and multivariate analysis and report standardized ß coefficients with 95% confidence intervals (CI). KEY RESULTS: The regression model revealed that the overall prevalence of DGBI was inversely associated with both GDP per capita (ß = -0.57, 95% CI: -0.92, -0.22, p = 0.002) and happiness scores (ß = -0.433 95% CI: 0.821, -0.065, p = 0.023), while being positively associated with H. pylori prevalence (ß = 0.40, 95% CI: 0.008, 0.81, p = 0.046). The prevalence of functional constipation (FC) was also inversely associated with GDP per capita (ß = -0.50, 95% CI: -0.86, -0.13, p = 0.01) and happiness scores (ß = -0.497, 95% CI: -0.863, -0.132, p = 0.01), while being positively associated with H. pylori prevalence (ß = 0.53, 95% CI: 0.16, 0.91, p = 0.007). The Multivariate model analysis revealed that combining the factors of H. pylori prevalence, suicide rate, household size and happiness scores showed statistically significant association with FC (p = 0.039). Household size (ß = -0.43, 95% CI: -0.82, 0.038, p = 0.033) and suicide rates (ß = 0.55, 95% CI: 0.19, 0.90, p = 0.004) were statistically significantly associated with functional diarrhea. Irritable bowel syndrome (IBS) was associated with GDP per capita (ß = -0.40, 95% CI: -0.79, -0.014, p = 0.043) and happiness scores (ß = -0.390, 95% CI: -0.778, -0.003, p = 0.049). CONCLUSIONS & INFERENCES: Utilizing publicly available data, the prevalence of DGBI across diverse countries is linked to various socio-cultural and environmental factors. Collectively, the data suggests that the prevalence of DGBI is increased in less prosperous regions of the world.

The COVID-19 pandemic as a modifier of DGBI symptom severity: A systematic review and meta-analysis.

BACKGROUND: This SRMA reviewed and assessed the changes in the severity of disorders of gut-brain interaction (DGBI) symptoms during the COVID-19 pandemic, and evaluated factors associated with symptom severity changes. METHODS: Electronic databases were searched until February 2024, for articles reporting on changes in symptom severity in DGBI patients during the COVID-19 pandemic. The proportion of DGBI patients who reported a change in their symptom severity were pooled using a random-effects model, and subgroup analyses were conducted to assess the effect of socio-cultural modifiers on symptom severity in DGBI. KEY RESULTS: Twelve studies including 3610 DGBI patients found that 31.4% (95% CI, 15.9-52.5) of DGBI patients experienced symptom deterioration, while 24.3% (95% CI, 10.2-47.5) experienced improvement. Countries with high gross domestic product (GDP) had a 43.5% (95% CI, 16.3-75.2) likelihood of symptom deterioration, compared to 9.2% (95% CI, 1.4-42.2) in lower GDP countries. Similarly, countries with low COVID fatality rates had a 60.1% (95% CI, 19.7-90.3) likelihood of symptom deterioration, compared to 18.3% (95% CI, 7.8-36.9) in higher fatality rate countries. Countries with lenient COVID policies had a 58.4% (95% CI, 14.1-92.3) likelihood of symptom deterioration, compared to 19% (95% CI, 8.2-38.1) in countries with stricter policies. Patients in high vaccine hesitancy countries had a 51.4% (95% CI, 19.5-82.2) likelihood of symptom deterioration, compared to 10.6% (95% CI, 2.7-33.4) in low vaccine hesitancy countries. CONCLUSIONS & INFERENCES: This meta-analysis reveals that a significantly higher proportion of DGBI patients experienced deterioration of symptoms during the COVID-19 pandemic. Various sociocultural, economic and environmental factors potentially modify the effects of the COVID-19 pandemic on DGBI.

Face-to-face interviews versus Internet surveys: Comparison of two data collection methods in the Rome foundation global epidemiology study: Implications for population-based research.

BACKGROUND AND AIMS: The Rome Foundation Global Epidemiology Study (RFGES) assessed the prevalence, burden, and associated factors of Disorders of Gut-Brain Interaction (DGBI) in 33 countries around the world. Achieving worldwide sampling necessitated use of two different surveying methods: In-person household interviews (9 countries) and Internet surveys (26 countries). Two countries, China and Turkey, were surveyed with both methods. This paper examines the differences in the survey results with the two methods, as well as likely reasons for those differences. METHODS: The two RFGES survey methods are described in detail, and differences in DGBI findings summarized for household versus Internet surveys globally, and in more detail for China and Turkey. Logistic regression analysis was used to elucidate factors contributing to these differences. RESULTS: Overall, DGBI were only half as prevalent when assessed with household vs Internet surveys. Similar patterns of methodology-related DGBI differences were seen within both China and Turkey, but prevalence differences between the survey methods were dramatically larger in Turkey. No clear reasons for outcome differences by survey method were identified, although greater relative reduction in bowel and anorectal versus upper gastrointestinal disorders when household versus Internet surveying was used suggests an inhibiting influence of social sensitivity. CONCLUSIONS: The findings strongly indicate that besides affecting data quality, manpower needs and data collection time and costs, the choice of survey method is a substantial determinant of symptom reporting and DGBI prevalence outcomes. This has important implications for future DGBI research and epidemiological research more broadly.

A comparative study of disorders of gut-brain interaction in Western Europe and Asia based on the Rome foundation global epidemiology study.

OBJECTIVE: Many studies have been published on disorders of the gut-brain interaction (DGBI) in Asia and Western Europe, but no previous study has directly assessed the difference between the two regions. The aim was to compare the prevalence of DGBI in Asia and Western Europe. METHODS: We used data collected in a population-based Internet survey, the Rome Foundation Global Epidemiology Study, from countries in Western Europe (Belgium, France, Germany, Netherlands, Italy, Spain, Sweden, and the United Kingdom) and Asia (China, Japan, South Korea, and Singapore). We assessed DGBI diagnoses (Rome IV Adult Diagnostic Questionnaire), anxiety/depression (Patient Health Questionnaire-4, PHQ-4), non-GI somatic symptoms (PHQ-12), and access to and personal costs of doctor visits. RESULTS: The study included 9487 subjects in Asia and 16,314 in Western Europe. Overall, 38.0% had at least one DGBI; younger age, female sex, and higher scores on PHQ4 and PHQ12 were all associated with DGBI. The prevalence of having at least one DGBI was higher in Western Europe than in Asia (39.1% vs 36.1%, OR 1.14 [95% CI 1.08-1.20]). This difference was also observed for DGBI by anatomical regions, most prominently esophageal DGBI (OR 1.67 [1.48-1.88]). After adjustment, the difference in DGBI prevalence diminished and psychological (PHQ-4) and non-GI somatic symptoms (PHQ-12) had the greatest effect on the odds ratio estimates. CONCLUSION: The prevalence of DGBI is generally higher in Western Europe compared to Asia. A considerable portion of the observed difference in prevalence rates seems to be explained by more severe psychological and non-GI somatic symptoms in Western Europe.

Guidance on performance and reporting of high-resolution oesophageal manometry and ambulatory pH monitoring in Singapore.

INTRODUCTION: We aimed to provide a practical and evidence-based guide on the indications, performance and reporting of high-resolution oesophageal manometry (HRM) and ambulatory pH monitoring (PHM) in adult patients in Singapore. METHODS: The guideline committee comprised local gastroenterologists from public and private sectors with particular expertise in aspects of HRM and PHM, and it was tasked to produce evidence-based statements on the indications, performance and reporting of these tests. Each committee member performed literature searches to retrieve relevant articles within the context of domains to which they were assigned. RESULTS: Twelve recommendation statements were created and summarised. CONCLUSION: Standardising key aspects of HRM and PHM is imperative to ensure the delivery of high-quality care. We reported the development of recommendations for the performance and interpretation of HRM and ambulatory reflux monitoring in Singapore.

SAGES guidelines for the use of peroral endoscopic myotomy (POEM) for the treatment of achalasia.

BACKGROUND: Peroral endoscopic myotomy (POEM) is increasingly used as primary treatment for esophageal achalasia, in place of the options such as Heller myotomy (HM) and pneumatic dilatation (PD) OBJECTIVE: These evidence-based guidelines from the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) intend to support clinicians, patients and others in decisions about the use of POEM for treatment of achalasia. RESULTS: The panel agreed on 4 recommendations for adults and children with achalasia. CONCLUSIONS: Strong recommendation for the use of POEM over PD was issued unless the concern of continued postoperative PPI use remains a key decision-making concern to the patient. Conditional recommendations included the option of using either POEM or HM with fundoplication to treat achalasia, and favored POEM over HM for achalasia subtype III.

Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study.

BACKGROUND & AIMS: Although functional gastrointestinal disorders (FGIDs), now called disorders of gut-brain interaction, have major economic effects on health care systems and adversely affect quality of life, little is known about their global prevalence and distribution. We investigated the prevalence of and factors associated with 22 FGIDs, in 33 countries on 6 continents. METHODS: Data were collected via the Internet in 24 countries, personal interviews in 7 countries, and both in 2 countries, using the Rome IV diagnostic questionnaire, Rome III irritable bowel syndrome questions, and 80 items to identify variables associated with FGIDs. Data collection methods differed for Internet and household groups, so data analyses were conducted and reported separately. RESULTS: Among the 73,076 adult respondents (49.5% women), diagnostic criteria were met for at least 1 FGID by 40.3% persons who completed the Internet surveys (95% confidence interval [CI], 39.9-40.7) and 20.7% of persons who completed the household surveys (95% CI, 20.2-21.3). FGIDs were more prevalent among women than men, based on responses to the Internet survey (odds ratio, 1.7; 95% CI, 1.6-1.7) and household survey (odds ratio, 1.3; 95% CI, 1.3-1.4). FGIDs were associated with lower quality of life and more frequent doctor visits. Proportions of subjects with irritable bowel syndrome were lower when the Rome IV criteria were used, compared with the Rome III criteria, in the Internet survey (4.1% vs 10.1%) and household survey (1.5% vs 3.5%). CONCLUSIONS: In a large-scale multinational study, we found that more than 40% of persons worldwide have FGIDs, which affect quality of life and health care use. Although the absolute prevalence was higher among Internet respondents, similar trends and relative distributions were found in people who completed Internet vs personal interviews.

Esophageal motility disorders on high-resolution manometry: Chicago classification version 4.0©.

Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). Fifty-two diverse international experts separated into seven working subgroups utilized formal validated methodologies over two-years to develop CCv4.0. Key updates in CCv.4.0 consist of a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, a refined definition of esophagogastric junction (EGJ) outflow obstruction (EGJOO), more stringent diagnostic criteria for ineffective esophageal motility and description of baseline EGJ metrics. Further, the CCv4.0 sought to define motility disorder diagnoses as conclusive and inconclusive based on associated symptoms, and findings on provocative testing as well as supportive testing with barium esophagram with tablet and/or functional lumen imaging probe. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of peristalsis and obstruction at the EGJ.

The international anorectal physiology working group (IAPWG) recommendations: Standardized testing protocol and the London classification for disorders of anorectal function.

BACKGROUND: This manuscript summarizes consensus reached by the International Anorectal Physiology Working Group (IAPWG) for the performance, terminology used, and interpretation of anorectal function testing including anorectal manometry (focused on high-resolution manometry), the rectal sensory test, and the balloon expulsion test. Based on these measurements, a classification system for disorders of anorectal function is proposed. METHODS: Twenty-nine working group members (clinicians/academics in the field of gastroenterology, coloproctology, and gastrointestinal physiology) were invited to six face-to-face and three remote meetings to derive consensus between 2014 and 2018. KEY RECOMMENDATIONS: The IAPWG protocol for the performance of anorectal function testing recommends a standardized sequence of maneuvers to test rectoanal reflexes, anal tone and contractility, rectoanal coordination, and rectal sensation. Major findings not seen in healthy controls defined by the classification are as follows: rectoanal areflexia, anal hypotension and hypocontractility, rectal hyposensitivity, and hypersensitivity. Minor and inconclusive findings that can be present in health and require additional information prior to diagnosis include anal hypertension and dyssynergia. CONCLUSIONS AND INFERENCES: This framework introduces the IAPWG protocol and the London classification for disorders of anorectal function based on objective physiological measurement. The use of a common language to describe results of diagnostic tests, standard operating procedures, and a consensus classification system is designed to bring much-needed standardization to these techniques.

Chronic Constipation and Constipation-Predominant IBS: Separate and Distinct Disorders or a Spectrum of Disease?

Rome III diagnostic criteria separate patients with idiopathic chronic constipation into mutually exclusive categories of constipation-predominant irritable bowel syndrome (IBS-C) or functional constipation (FC). However, several experts think that these conditions are not different disorders, but parts of a continuum. To shed light on this issue, we examined studies that compared IBS-C with FC with respect to symptoms, pathophysiologic mechanisms, and treatment response. When the Rome III requirement that patients meeting criteria for IBS cannot also be given a diagnosis of FC is suspended, most patients meet criteria for both, and, contrary to expectation, IBS-C patients have more symptoms of constipation than patients with FC. No symptoms reliably separate IBS-C from FC. Physiologic tests are not reliably associated with diagnosis, but visceral pain hypersensitivity tends to be more strongly associated with IBS-C than with FC, and delayed colonic transit tends to be more common in FC. Although some treatments are effective for both IBS-C and FC, such as prosecretory agents, other treatments are specific to IBS-C (eg, antidepressants, antispasmodics, cognitive behavior therapy) or FC (eg, prucalopride, biofeedback). Future studies should permit IBS-C and FC diagnoses to overlap. Physiologic tests comparing these disorders should include visceral pain sensitivity, colonic transit time, time to evacuate a water-filled balloon, and anal pressures or electromyographic activity from the anal canal. To date, differential responses to treatment provide the strongest evidence that IBS-C and FC may be different disorders, rather than parts of a spectrum.

Partner Burden: A Common Entity in Celiac Disease.

BACKGROUND: Caregiver burden is documented in several chronic diseases, but it has not been investigated in celiac disease (CD). AIMS: We aim to quantify the burden to partners of CD patients and identify factors that affect the perceived burden. METHODS: We surveyed patients with biopsy-proven CD and their partners. Patients completed CD-specific questions, including the validated Celiac Symptom Index (CSI) survey. Partners completed the validated Zarit Burden Interview (ZBI) and questions regarding sexual and relationship satisfaction. Univariable and multivariable analyses were used to assess the association between demographics, CD characteristics, and partner burden. RESULTS: In total, 94 patient/partner pairs were studied. Fifteen patients (16 %) reported a CSI score associated with a poor quality of life, and 34 partners (37 %) reported a ZBI score corresponding to mild-to-moderate burden. Twenty-two partners (23 %) reported moderate-to-low overall relationship satisfaction, and 12 (14 %) reported moderate-to-low sexual satisfaction. The degree of partner burden was directly correlated with patient CSI score (r = 0.27; p = 0.008), and there were moderate-to-strong inverse relationships between partners' burden and relationship quality (r = -0.70; p < 0.001) and sexual satisfaction (r = -0.42; p < 0.001). On multivariable logistic regression, predictors of mild-to-moderate partner burden were low partner relationship satisfaction (OR 17.06, 95 % CI 2.88-101.09, p = 0.002) and relationship duration ≥10 years (OR 14.42, 95 % CI 1.69-123.84, p = 0.02). CONCLUSIONS: Partner burden is common in CD, with more than one-third of partners experiencing mild-to-moderate burden. Partner burden is directly correlated with patient symptom severity, and it increases with poorer sexual and relationship satisfaction. Healthcare providers should address relationship factors in their care of patients with CD.

Visceral pain perception in patients with irritable bowel syndrome and healthy volunteers is affected by the MRI scanner environment.

BACKGROUND: The MRI scanner environment induces marked psychological effects, but specific effects on pain perception and processing are unknown and relevant to all brain imaging studies. OBJECTIVES AND METHODS: We performed visceral and somatic quantitative sensory and pain testing and studied endogenous pain modulation by heterotopic stimulation outside and inside the functional MRI scanner in 11 healthy controls and 13 patients with irritable bowel syndrome. RESULTS: Rectal pain intensity (VAS 0-100) during identical distension pressures increased from 39 (95% confidence interval: 35-42) outside the scanner to 53 (43-63) inside the scanner in irritable bowel syndrome, and from 42 (31-52) to 49 (39-58), respectively, in controls (ANOVA for scanner effect: p = 0.006, group effect: p = 0.92). The difference in rectal pain outside versus inside correlated significantly with stress (r = -0.76, p = 0.006), anxiety (r = -0.68, p = 0.02) and depression scores (r = -0.67, p = 0.02) in controls, but not in irritable bowel syndrome patients, who a priori had significantly higher stress and anxiety scores. ANOVA analysis showed trends for effect of the scanner environment and subject group on endogenous pain modulation (p = 0.09 and p = 0.1, respectively), but not on somatic pain (p > 0.3). CONCLUSION: The scanner environment significantly increased visceral, but not somatic, pain perception in irritable bowel syndrome patients and healthy controls in a protocol specifically aimed at investigating visceral pain. Psychological factors, including anxiety and stress, are the likely underlying causes, whereas classic endogenous pain modulation pathways activated by heterotopic stimulation play a lesser role. These results are highly relevant to a wide range of imaging applications and need to be taken into account in future pain research. Further controlled studies are indicated to clarify these findings.

Prevalence of Irritable Bowel Syndrome in Singapore and Its Association with Dietary, Lifestyle, and Environmental Factors.

BACKGROUND/AIMS: The prevalence of irritable bowel syndrome (IBS) has risen considerably over the past decade in Singapore. We aim to explore the contribution of changes in diet, lifestyle and habits that may contribute to the increased prevalence and development of IBS. METHODS: This is a survey-based cross-sectional population study aimed to gather demographic, socio-economical, lifestyle, dietary, antibiotic usage and other related information. Subjects were adult male or female Singaporeans aged 21 years or above. Association of the factors gathered with the presence or absence of IBS (by Rome III criteria) was assessed using chi-square or Fisher's exact test. Variables with a level of statistical significance of 0.1 or less in the univariate analysis were entered into a stepwise logistic regression model. RESULTS: A total of 297 subjects participated in the study (female 60.3%). Overall, 20.9% subjects fulfilled the Rome III IBS criteria. Univariate analysis showed that IBS was associated with pet ownership, antibiotic usage, late dinner, (> 9 PM) and consumption of Western meals, coffee, and bread. The multivariate logistic regression analyses showed that IBS was independently associated with being a pet owner (P = 0.008; OR, 2.5; 95% CI, 1.278-5.037). CONCLUSIONS: The prevalence of IBS was 20.9% using the Rome III criteria in our study. The association between IBS and pet ownership will need further investigation.

Gastrointestinal Symptoms and Altered Intestinal Permeability Induced by Combat Training Are Associated with Distinct Metabotypic Changes.

Physical and psychological stress have been shown to modulate multiple aspects of gastrointestinal (GI) physiology, but its molecular basis remains elusive. We therefore characterized the stress-induced metabolic phenotype (metabotype) in soldiers during high-intensity combat training and correlated the metabotype with changes in GI symptoms and permeability. In a prospective, longitudinal study, urinary metabotyping was conducted on 38 male healthy soldiers during combat training and a rest period using gas chromatography-mass spectrometry. The urinary metabotype during combat training was clearly distinct from the rest period (partial least-squares discriminant analysis (PLSDA) Q(2) = 0.581), confirming the presence of a unique stress-induced metabotype. Differential metabolites related to combat stress were further uncovered, including elevated pyroglutamate and fructose, and reduced gut microbial metabolites, namely, hippurate and m-hydroxyphenylacetate (p < 0.05). The extent of pyroglutamate upregulation exhibited a positive correlation with an increase in IBS-SSS in soldiers during combat training (r = 0.5, p < 0.05). Additionally, the rise in fructose levels was positively correlated with an increase in intestinal permeability (r = 0.6, p < 0.005). In summary, protracted and mixed psychological and physical combat-training stress yielded unique metabolic changes that corresponded with the incidence and severity of GI symptoms and alteration in intestinal permeability. Our study provided novel molecular insights into stress-induced GI perturbations, which could be exploited for future biomarker research or development of therapeutic strategies.

Massive gastrointestinal hemorrhage secondary to typhoid colitis: A case report and literature review.

We present a case of massive lower gastrointestinal hemorrhage secondary to Salmonella enterica subtype Typhi (S. Typhi) colitis, in a 29 year-old female treated for S. Typhi bacteremia. One week post-treatment, she unexpectedly developed a large volume of rectal bleeding. Endoscopy showed colonic ulcers and ileitis, but no endoscopic hemostasis was required. Treatment was supportive with transfusions and a prolonged course of antimicrobials, with the bleeding stopping spontaneously. This case illustrates the phenomenon of delayed lower gastrointestinal hemorrhage, as a rare complication of S. Typhi infection.

Melatonin regulation as a possible mechanism for probiotic (VSL#3) in irritable bowel syndrome: a randomized double-blinded placebo study.

BACKGROUND: Probiotics have treatment efficacy in irritable bowel syndrome (IBS), but the exact mechanism remains obscure. One hypothesis is the mediation of melatonin levels, leading to changes in IBS symptoms. AIM: The purpose of this study was to evaluate the effects of a probiotic, VSL#3, on symptoms, psychological and sleep parameters, and pain sensitivity in IBS, and relate these parameters to in vivo melatonin levels. METHODS: Forty-two IBS patients were randomly assigned to receive VSL#3 or placebo for 6 weeks. Subjects completed bowel and psychological questionnaires, underwent rectal sensitivity testing and saliva melatonin assays. RESULTS: Abdominal pain duration and distension intensity decreased significantly in the probiotic group, along with an increase in rectal distension pain thresholds. A correlation between increase in pain tolerance and improvement in abdominal pain scores (r = 0.51, p = 0.02) was seen with probiotic. There was an increase in salivary morning melatonin levels in males treated with VSL#3, which correlated (r = 0.61) with improved satisfaction in bowel habits. When grouped based on baseline diurnal melatonin levels, patients with normal diurnal fluctuations showed an increase in morning melatonin levels with VSL#3 treatment, which significantly correlated with improved satisfaction in bowel habits (r = 0.68). They also had reduced symptom severity scores and abdominal pain duration when treated with VSL#3, as well as satisfaction with bowel movements and quality-of-life. CONCLUSIONS: VSL#3 improved symptoms and increased rectal pain thresholds. Symptom improvement correlated with a rise in morning melatonin, significant in males and subjects with normal circadian rhythm. This suggests that probiotics may act by influencing melatonin production, hence modulating IBS symptoms, in individuals with a normal circadian rhythm.

Fructose transporters GLUT5 and GLUT2 expression in adult patients with fructose intolerance.

BACKGROUND: Gastrointestinal symptoms and malabsorption following fructose ingestion (fructose intolerance) are common in functional gastrointestinal disorders (FGID). The underlying mechanism is unclear, but is hypothesized to be related an abnormality of intestinal fructose transporter proteins. OBJECTIVE: To assess the expression of the main intestinal fructose transporter proteins, glucose transport protein 5 (GLUT5) and 2 (GLUT2), in FGID. METHODS: The expression of GLUT5 and GLUT2 protein and mRNA in small intestinal biopsy tissue was investigated using real-time reverse-transcription PCR and Western immunoblotting in 11 adults with FGID and fructose intolerance ascertained by breath testing and in 15 controls. RESULTS: Median expression levels of GLUT5 mRNA normalized to beta-actin were 0.18 (interquartile range, IQR, 0.13-0.21) in patients and 0.17 (IQR 0.12-0.19) in controls (p > 0.05). Respective levels of GLUT2 mRNA were 0.26 (IQR 0.20-0.31) and 0.26 (IQR 0.19-0.31) (p > 0.05). Median expression levels of GLUT5 protein normalized to alpha-tubulin were 0.95 (IQR 0.52-1.68) in patients and 0.95 (IQR 0.59-1.15) in controls (p > 0.05). Respective protein expression levels for GLUT2 were 1.56 (IQR 1.06-2.14) and 1.35 (IQR 0.96-1.79) (p > 0.05). CONCLUSIONS: Human fructose intolerance may not be associated with marked changes in GLUT5 and GLUT2 expression. Replication of these results in a larger subject group, including measures of transporter activation and membrane and subcellular localization, is warranted.

Combat-training stress in soldiers increases S100B, a marker of increased blood-brain-barrier permeability, and induces immune activation.

BACKGROUND: Experimental data suggest stress-related cognitive dysfunction may be associated with increased blood-brain-barrier (BBB) permeability secondary to immune activation. METHODS: We investigated the relationship between prolonged and intense physical and psychological combat-training stress, immune activation and blood-brain-barrier permeability in 37 healthy male army medical rapid response troops. RESULTS: Soldiers during intense combat training showed greater self-reported stress, anxiety and depression levels than at rest, as assessed by specific questionnaires. S100B, a marker of BBB permeability, as well as serum cortisol, IL-6 and TNF-α concentrations, were significantly increased in soldiers during combat training compared to rest (all p<0.05). Serum S100B correlated negatively with morning serum cortisol in soldiers during combat training, but not during the rest period (r=-0.387, p<0.05). CONCLUSION: We conclude that combat training inducing significant levels of stress, depression and anxiety is accompanied by evidence of increased blood-brain barrier permeability and by increases in systemic pro-inflammatory mediators.

Gender differences in predictors of colorectal cancer screening uptake: a national cross sectional study based on the health belief model.

BACKGROUND: Colorectal Cancer (CRC) is rapidly rising in Asia, but screening uptake remains poor. Although studies have reported gender differences in screening rates, there have been few studies assessing gender specific perceptions and barriers towards CRC screening, based on behavioral frameworks. We applied the Health Belief Model to identify gender-specific predictors of CRC screening in an Asian population. METHODS: A nationwide representative household survey was conducted on 2000 subjects aged 50 years and above in Singapore from 2007 to 2008. Screening behaviour, knowledge and beliefs on CRC screening were assessed by face-to-face structured interviews. The response rate was 88.2%. RESULTS: 26.7 percent had undergone current CRC screening with no gender difference in rates. Almost all agreed that CRC would lead to suffering (89.8%), death (84.6%) and would pose significant treatment cost and expense (83.1%). The majority (88.5%) agreed that screening aids early detection and cure but only 35.4% felt susceptible to CRC. Nearly three-quarters (74.3%) of the respondents recalled reading or hearing information on CRC in the print or broadcast media. However, only 22.6% were advised by their physicians to undergo screening. Significantly more women than men had feared a positive diagnosis, held embarrassment, pain and risk concerns about colonoscopy and had friends and family members who encouraged screening. On multivariate analysis, screening uptake showed a positive association with worry about contracting CRC and a physician's recommendation and a negative association with perceived pain about colonoscopy for both genders. For women only, screening was positively associated with having attended a public talk on CRC and having a family member with CRC, and was negatively associated with Malay race and perceived danger of colonoscopy. CONCLUSIONS: CRC screening remains poor despite high levels of awareness of its benefits in this Asian population. Race, worry about contracting cancer, psychological barriers, and cues from the doctor and a public talk on CRC were associated with screening with gender specific differences. Strategies to increase CRC screening uptake should consider gender specific approaches to address psychological barriers and increase disease susceptibility through public health education and active promotion by physicians.