Cross-sectional association of continuous glucose monitoring-derived metrics with cerebral small vessel disease in older adults with type 2 diabetes.

AIM: To examine cross-sectional associations between continuous glucose monitoring (CGM)-derived metrics and cerebral small vessel disease (SVD) in older adults with type 2 diabetes. MATERIALS AND METHODS: In total, 80 patients with type 2 diabetes aged ≥70 years were analysed. Participants underwent CGM for 14 days. From the CGM data, we derived mean sensor glucose, percentage glucose coefficient of variation, mean amplitude of glucose excursion, time in range (TIR, 70-180 mg/dl), time above range (TAR) and time below range metrics, glycaemia risk index and high/low blood glucose index. The presence of cerebral SVD, including lacunes, microbleeds, enlarged perivascular spaces and white matter hyperintensities, was assessed, and the total number of these findings comprised the total cerebral SVD score (0-4). Ordinal logistic regression analyses were performed to examine the association of CGM-derived metrics with the total SVD score. RESULTS: The median SVD score was 1 (interquartile range 0-2). Higher hyperglycaemic metrics, including mean sensor glucose, TAR >180 mg/dl, TAR >250 mg/dl, and high blood glucose index and glycaemia risk index, were associated with a higher total SVD score. In contrast, a higher TIR (per 10% increase) was associated with a lower total SVD score (odds ratio 0.73, 95% confidence interval 0.56-0.95). Glycated haemoglobin, percentage glucose coefficient of variation, mean amplitude of glucose excursions, time below range and low blood glucose index were not associated with total cerebral SVD scores. CONCLUSIONS: The hyperglycaemia metrics and TIR, derived from CGM, were associated with cerebral SVD in older adults with type 2 diabetes.

Cross-sectional association of metrics derived from continuous glucose monitoring with cognitive performance in older adults with type 2 diabetes.

AIM: To examine the association between continuous glucose monitoring (CGM)-derived metrics and cognitive performance in older adults with type 2 diabetes (T2D). MATERIALS AND METHODS: A total of 100 outpatients with T2D aged 70 years or older were analysed. Participants underwent CGM for 14 days. As CGM-derived metrics, mean sensor glucose (SG), glucose coefficient of variation (CV), time in range (TIR; 70-180 mg/dl), time above range (TAR; > 180 mg/dl) and time below range (TBR; < 70 mg/dl), were calculated. Participants underwent cognitive tests, including the Japanese version of the Montreal Cognitive Assessment (MoCA-J), a delayed word-recall test from the Alzheimer's Disease Assessment Scale-cognitive subscale, a digit symbol substitution test, a letter word fluency test, a trail-making test (TMT) and digit span test (DSP). RESULTS: In multiple regression analyses adjusted for confounders, a higher mean SG was associated with a lower performance in MoCA-J and TMT part B (TMT-B) (P < .05). A higher TAR was associated with a lower performance in TMT-B and DSP-backward (P < .05). By contrast, a higher TIR was associated with better function in TMT-B and DSP-backward (P < .05). Furthermore, CV and TBR were not associated with any cognitive function. CONCLUSION: Hyperglycaemia metrics and TIR derived from CGM are associated with cognitive functions, especially with executive function and working memory, in older adults with T2D.

Associations between motorized transport access, out-of-home activities, and life-space mobility in older adults in Japan.

BACKGROUND: Motorized transport access and out-of-home activities are two potential correlates of Life-space mobility (LSM), a common research topic in mobility studies of older adults. These correlates remain mostly unexplored in previous literature and relating them with LSM can reveal directions for improving the LSM of older adults. METHODS: The associations between motorized transport access, out-of-home activities, and LSM were examined using data from 1,333 older adults (mean age = 70.63) living in 15 cities and towns in Japan. LSM was assessed using composite life-space assessment (LSA) scores. Motorized transport access was measured using dummies showing whether a person had car access (divided into five levels) and used public transport (bus and railway), and out-of-home activities were measured using the number of various activities that were conducted during the most recent weekday and weekend day. Generalized linear models were used to assess the associations. RESULTS: The sample was dominated by males (74.42%), with more than half of the sample had their own cars. On average, each respondent had four activities during two survey days, and shopping was the most common activity. The results showed that owning a car and using railway, as well as various activities were associated with increased composite LSA scores, whereas no cars or only shared cars in home were associated with decreased composite LSA scores. However, these associations differed between males and females. CONCLUSIONS: In this study, different levels of motorized transport access and different types of out-of-home activities were found to associate differently with composite LSA scores. Based on these findings, we suggest that policymakers should provide more transport access, pay more attention to the LSM of older adults with high clinics/hospital activities, and trigger more shopping and daily leisure activities for older adults to improve the LSM of this population.

The Relationship between Changes in Organ-Tissue Mass and Sleeping Energy Expenditure Following Weight Change in College Sumo Wrestlers.

Background and objectives: It has been well established that the resting energy expenditure (REE) for the whole body is the sum of the REE for each organ-tissue in young and middle-aged healthy adults. Based on these previous studies, although it is speculated that sleeping energy expenditure (SEE, which has small inter-individual variability) changes with a commensurate gain or reduction in the resting metabolic rate of each organ-tissue, it is unclear whether a change in organ-tissue masses is directly attributed to the fluctuation of SEE at present. This study aimed to assess the relationship between changes in organ-tissue mass and sleeping energy expenditure (SEE) following weight change in college Sumo wrestlers. This included blood analysis, which is related to energy expenditure. Materials and Methods: A total of 16 healthy male college Sumo wrestlers were recruited in this study. All measurements were obtained before and after weight change. Magnetic resonance imaging measurements were used to determine the volume of the skeletal muscle (SM), liver, and kidneys, and an indirect human calorimeter was used to determine SEE before and after weight change. Results: The change in body mass and SEE ranged between -8.7~9.5 kg, and -602~388 kcal/day. Moreover, changes in SM, liver, and kidneys ranged between -3.3~3.6 kg, -0.90~0.77 kg, and -0.12~0.07 kg. The change in SEE was not significantly correlated with the change in SM or liver mass, nor with blood analyses; however, a significant relationship between the change in kidney mass and SEE was observed. Conclusions: Based on our results, there is a possibility that the mass of the kidneys has an effect on the change in SEE following weight change in college Sumo wrestlers.

Estimating metabolic equivalents for activities in daily life using acceleration and heart rate in wearable devices.

BACKGROUND: Herein, an algorithm that can be used in wearable health monitoring devices to estimate metabolic equivalents (METs) based on physical activity intensity data, particularly for certain activities in daily life that make MET estimation difficult. RESULTS: Energy expenditure data were obtained from 42 volunteers using indirect calorimetry, triaxial accelerations and heart rates. The proposed algorithm used the percentage of heart rate reserve (%HRR) and the acceleration signal from the wearable device to divide the data into a middle-intensity group and a high-intensity group (HIG). The two groups were defined in terms of estimated METs. Evaluation results revealed that the classification accuracy for both groups was higher than 91%. To further facilitate MET estimation, five multiple-regression models using different features were evaluated via leave-one-out cross-validation. Using this approach, all models showed significant improvements in mean absolute percentage error (MAPE) of METs in the HIG, which included stair ascent, and the maximum reduction in MAPE for HIG was 24% compared to the previous model (HJA-750), which demonstrated a 70.7% improvement ratio. The most suitable model for our purpose that utilized heart rate and filtered synthetic acceleration was selected and its estimation error trend was confirmed. CONCLUSION: For HIG, the MAPE recalculated by the most suitable model was 10.5%. The improvement ratio was 71.6% as compared to the previous model (HJA-750C). This result was almost identical to that obtained from leave-one-out cross-validation. This proposed algorithm revealed an improvement in estimation accuracy for activities in daily life; in particular, the results included estimated values associated with stair ascent, which has been a difficult activity to evaluate so far.

Association of physical activity and appetite with visual function related to driving competence in older adults.

BACKGROUND: Older people are at greater risk of traffic accidents, partially because of age-related declines in visual function, including reduced useful field of view (UFOV). However, lifestyle factors which cause age-related decline in UFOV remain poorly understood. We conducted a study to investigate whether physical activity and appetite status were related to UFOV test performance in healthy older adults. METHODS: Thirty community-dwelling older people (age 68.6 ± 3.1 years, 15 females) were enrolled in this study. Each participant completed the Council on Nutrition appetite questionnaire (CNAQ) and a UFOV test. They then wore a tri-axial accelerometer (Active style Pro HJA-350IT) for 3-6 consecutive days to objectively measure their PA in free-living conditions. RESULTS: Longer time spent in vigorous physical activity was significantly associated with better UFOV test performance when adjusted for age and accelerometer wear time (non-locomotive: r = -0.435, locomotive: r = -0.449; n = 25). In addition, male, but not female, participants with a higher CNAQ score had significantly better UFOV test performance in both an unadjusted model (r = -0.560; n = 15) and a model adjusted for age (r = -0.635; n = 15). CONCLUSIONS: The results suggest that appetite status among males and time spent in high intensity PA are associated with visual function related to driving competence in older adults.

Suitability of surveillance colonoscopy for patients with ulcerative colitis to detect colorectal cancer: current guidelines miss some early-stage cases.

Surveillance colonoscopy (SC) is considered important for the early detection and treatment of colorectal cancer (CRC) in patients with ulcerative colitis (UC). Here, we investigated whether current guidelines are appropriate in preventing UC patients from being diagnosed with CRC at an incurable stage. Among 1583 patients under treatment for UC, 27 patients were diagnosed with CRC. Of these, we excluded two patients who had not undergone colonoscopy before CRC diagnosis. We then divided the remaining patients into three groups based on colonoscopy interval (A, 1 year or less; B, between 1 and 2 years; and C, 2 years or longer). Fifteen patients had tubular adenocarcinomas, and 10 had other types (8 poorly differentiated adenocarcinomas, 1 mucinous adenocarcinoma, 1 endocrine cell carcinoma). Five (20%) of 25 patients developed CRC within 8 years after the onset of UC, of which one case was detected at stage IV. Six patients were classified into group A, 8 into group B, and 11 into group C. On distribution by histologic type, tubular adenocarcinomas were detected in stages 0 - II in 100% in group A, 100% in group B, and 57.1% in group C. In contrast, other types of carcinomas were detected in stage 0 - II in 100% in group A, 40% in group B, and 0% in group C. Current guideline recommendations for SC are not sufficient for the detection of early stage CRC in patients with UC. SC should be commenced earlier than recommended in the current guidelines and repeated annually.

Minimally invasive extraction of a foreign body from the small intestine using double-balloon endoscopy.

Double-balloon endoscopy (DBE) can be used to treat disorders of the small intestine and can also be used to retrieve foreign bodies from the small intestine without surgery. We describe the findings of 22 cases in which DBE was used to try and retrieve foreign bodies from the small intestine. The foreign bodies included 12 capsule endoscopes, 3 artificial teeth, 3 medical tubes, 2 worms, 1 press-through packet of medicine, and 1 intestinal stone. The retrieval success rate was 86.3% (19/22), and there were no complications related to the retrieval procedures. Snare forceps were the most useful device for grasping the foreign bodies, and DBE was usually performed via an oral route. If an anal route is selected in cases involving stenosis of the small intestine, endoscopic balloon dilation will be necessary to reach the target. In conclusion, DBE is very useful for extracting foreign bodies from the small intestine, and the careful selection of the DBE route and the removal device are important for successfully retrieving foreign bodies.

Clinical usefulness of novel tag-less Agile patency capsule prior to capsule endoscopy for patients with suspected small bowel stenosis.

BACKGROUND AND AIM: The Agile patency capsule (PC; Given Imaging Ltd, Yoqneam, Israel) is used as a dummy prior to capsule endoscopy (CE) to avoid retention of the CE capsule. However, impaction of the PC's inner radio frequency identification (RFID) tag in a stricture could cause small-bowel ileus. Recently, the RFID tag-less PC was introduced into clinical practice. Herein, we aimed to retrospectively evaluate the usefulness of the tag-less PC. METHODS: Of 154 patients who were scheduled to undergo CE, 100 consecutive patients (65%) who underwent PC evaluation were enrolled in the present study. Primary study end point was the retention rate of the CE capsule after successful passage of the PC. Secondary end point was analysis of the significant factors affecting the passage of the PC. RESULTS: In total, 87 patients (87%) had bowel patency confirmed by PC evaluation. There was no capsule retention in any of these 87 patients during CE. Abnormal findings were obtained from 60 CE, and 41 patients received new or modified treatment. Multivariate analysis of factors related to the confirmation of patency demonstrated that stenosis on imaging was the most influential factor (P = 0.002, odds ratio 16.387). The results confirmed that passage of the PC depends on stenosis on imaging. CONCLUSIONS: Use of the tag-less PC confirmed gastrointestinal tract patency for most of the patients who did not have stenosis on imaging and allowed estimation of the patency for patients who did have stenosis on imaging.

Suppressive action of acetate on interleukin-8 production via tubulin-α acetylation.

Acetate is the major short-chain fatty acid produced by commensal bacteria in the gut and is known as a nutrient source for epithelial cells of the mucosa. Acetate also suppresses interleukin (IL)-2 production in T cells by inhibiting nuclear factor of activated T cells (NFAT) nuclear translocation via tubulin-α acetylation. Using acetylation of tubulin-α as a biomarker, we have examined the influence of acetate in the large intestine. Because of high concentrations of acetate in fecal material, tubulin-α acetylation is dominant in the proximal large intestine relative to other sections of the large intestine and is induced in epithelial cells of the colonic mucosa. Flagellin stimulation induces IL-8 production in epithelial cells and acetate suppresses this IL-8 production via tubulin-α acetylation. Flagellin stimulation activates nuclear factor-κB, CREB and AP-1, but not NFAT. Of these transcription factors, acetate specifically inhibits AP-1 activation. Acetate impairs flagellin-induced activation of the Rap1-MEK-ERK-Elk-1 pathway with acetylation of tubulin-α that is bound to Rap1, resulting in reduced expression of c-Fos, a subunit of AP-1. These findings reveal a novel action of acetate via tubulin-α acetylation in epithelial cells of the colonic mucosa.

Simplified magnetic anchor-guided endoscopic submucosal dissection in dogs (with videos).

BACKGROUND: Magnetic anchor-guided endoscopic submucosal dissection (MAG-ESD) was developed to reduce adverse events such as bleeding and perforation and to facilitate ESD. However, the external electromagnet required miniaturization to make it suitable for daily clinical practice. OBJECTIVE: To evaluate the feasibility of simplified MAG-ESD using permanent magnets. DESIGN: Case series. SETTING: Nagoya University Hospital. SUBJECTS: Beagle dogs. INTERVENTIONS: The simplified MAG-ESD was performed on 10 representative areas of the stomachs of beagle dogs. The magnetic anchor consisted of an internal magnet attached to a hemoclip. The external and internal magnets were made from the rare earth neodymium. MAIN OUTCOME MEASUREMENTS: The feasibility of countertraction with good visualization using simplified MAG-ESD. The rate of perforation, the time required for preparation, and attaching the magnetic anchor were also evaluated. RESULTS: All lesions were successfully resected without perforation. The magnetic anchor could be controlled easily, and direct visualization was maintained by adequate counter traction. Preparing the magnetic anchor and grasping the mucosal edge using the hemoclip was easy and required a median of only 4 minutes (range, 2-7 minutes). LIMITATIONS: Animal experiment, low number and lesion size. CONCLUSIONS: This simplified MAG-ESD is feasible and allowed excellent visualization in the dog stomach. The feasibility of this system should be assessed in humans.

Usefulness of Helicobacter pylori eradication for precancerous lesions of the gastric remnant.

BACKGROUND AND AIM: Secondary stomach cancer in lesions of the remnant stomach occurs relatively soon after distal gastrectomy using the Billroth I reconstruction procedure. Prophylactic eradication of Helicobacter pylori after endoscopic resection of early gastric cancer should be used to prevent the development of metachronous gastric carcinoma. However, the effect of H. pylori eradication on the gastric remnant has not been clearly determined. METHODS: Eight patients who were H. pylori-positive after distal gastrectomy for primary gastric cancer underwent eradication therapy and were followed by endoscopy for 9 years. Upper gastroenteroscopy series were done before and at 1, 3, 5, 7 and 9 years after eradication, and biopsy specimens were taken from the lesser and greater curvatures, respectively. Histological changes, including chronic inflammation, activity, atrophy, and intestinal metaplasia, were evaluated using the updated Sydney system. RESULTS: Successful eradication was confirmed using the urea breath test in all eight patients. Chronic inflammation scores were improved after eradication at both the lesser (mean scores ± SD: before eradication, 2.9±0.5; 1 year after, 2.3±0.4; 3 years, 1.8±0.3; 5 years, 1.5±0.3; 7 years, 1.3±0.3; and 9 years, 1.0±0.3) and greater curvatures (before, 2.9±0.4; 1 year after, 1.9±0.3; 3 years, 1.4±0.4; 5 years, 1.3±0.3; 7 years, 1.1±0.2; and 9 years, 0.6±0.3). Atrophy scores improved more quickly after eradication than chronic inflammation scores at both the lesser (before, 2.4±0.5; 1 year after, 1.8±0.4; 3 years, 0.8±0.3; 5 years, 0.3±0.1; 7 years, 0.0; and 9 years, 0.0) and greater curvatures (before, 2.2±0.4; 1 year after, 1.3±0.3; 3 years, 0.5±0.3; 5 years, 0.0; 7 years, 0.0; and 9 years, 0.0). No secondary stomach cancers were found on endoscopy. CONCLUSIONS: Undergoing H. pylori eradication improved possible precancerous lesions of the gastric remnant among patients who had undergone distal gastrectomy. Prophylactic H. pylori eradication in the gastric remnant may be useful in preventing the development of metachronous gastric carcinoma.

Three cases with active bleeding from radiation enteritis that were diagnosed with video capsule endoscopy without retention.

Endoscopic exploration of the small bowel after pelvic radiation has limitations related to strong abdominal adhesion. It is often difficult to demonstrate the findings of radiation enteritis endoscopically, even with video capsule endoscopy (VCE) or double-balloon enteroscopy (DBE). We present our experience with three cases of radiation enteritis that were diagnosed using VCE and DBE, including their effective aspects. Radiation enteritis has not been diagnosed using conventional methods, and DBE may not accomplish deeper insertion into the ileum, although it is capable of both diagnosis and hemostasis. Therefore, VCE is thought to be the initial tool for the diagnosis of radiation enteritis when small bowel stenosis has not been previously detected and the risk of retention has been discussed.

Dietary macronutrient composition and its effect on 24-h substrate oxidation: A study of diurnal variations in carbohydrate and fat intake.

BACKGROUND & AIMS: In recent times, the complexity of food styles and meal content has increased, leading to significant variations in macronutrient composition between meals. This phenomenon has coincided with a rise in obesity rates. We aimed to determine whether a large variation in macronutrient composition between meals results in reduced fat oxidation. METHODS: A cross-over study was conducted with 13 healthy young men, using whole-body indirect calorimetry to test 24-h energy metabolic responses under three conditions: regular meals (R), high-carbohydrate breakfast (CB), or high-fat breakfast (FB), each with different macronutrient contents. The R condition included three meals daily with the same macronutrient composition. The CB condition included a high-carbohydrate meal at breakfast, high-fat meal at lunch, and high-carbohydrate meal at dinner. The FB condition included a high-fat meal at breakfast, high-carbohydrate meal at lunch, and high-carbohydrate meal at dinner. The daily macronutrient compositions were similar across the three conditions, except that CB and FB had larger variations in carbohydrate-fat balance between meals than R. The participants were tested in random order. During the dietary intervention, we compared 24-h whole-body metabolic parameters, including substrate oxidation (e.g., 24 h respiratory quotient [RQ]). RESULTS: No significant differences were observed in the measures of energy expenditure among the three conditions. However, after adjusting for the sleeping RQ on a preceding day, the estimated 24hRQ was lower under the FB condition (0.845) than under the R (0.854, P = 0.0077 vs. FB) and CB conditions (0.853, P = 0.016 vs. FB). No difference was observed in the magnitude of the 5-h RQ change from lunch to dinner under the CB condition and in the magnitude of change from breakfast to lunch under the FB condition. CONCLUSIONS: A large variation in the carbohydrate-fat balance between meals does not decrease daily fat oxidation. An FB may increase daily fat oxidation compared to a CB when the daily food quotient is constant, but this increase may not be owing to the upregulation of fat burning on a daily basis.

Investigation of seasonality of human spontaneous physical activity and energy expenditure in respiratory chamber in Phoenix, Arizona.

OBJECTIVE: The existence of seasonal changes in energy metabolism is uncertain. We investigated the relationship between the seasons and spontaneous physical activity (SPA), energy expenditure (EE), and other components measured in a respiratory chamber. METHODS: Between 1985-2005, 671 healthy adults (aged 28.8 ± 7.1 years; 403 men) in Phoenix, Arizona had a 24-hour stay in the respiratory chamber equipped with radar sensors; SPA (expressed as a percentage over the time interval), the energy cost of SPA, EE, and respiratory exchange ratio (RER) were measured. RESULTS: In models adjusted for known covariates, SPA (%) was lower during summer (7.2 ± 2.9, p = 0.0002), spring (7.5 ± 2.9, p = 0.025), and fall (7.6 ± 3, p = 0.038) compared to winter (8.3 ± 3.5, reference). Conversely, energy cost of SPA (kcal/h/%) was higher during summer (2.18 ± 0.83, p = 0.0008), spring (2.186 ± 0.83, p = 0.017), and fall (2.146 ± 0.75, p = 0.038) compared to winter (2.006 ± 0.76). Protein (292 ± 117 kcal/day, ß = -21.2, p = 0.08) oxidation rates was lower in the summer compared to winter. Carbohydrate and lipid oxidation rates (kcal/day) did not differ across seasons. RER and 24-h EE did not differ by season. CONCLUSION: SPA, representing fidgeting-like behavior in the chamber, demonstrated a winter peak and summer nadir in humans living in a desert climate. These findings indicate that the physiological propensity for movement may be affected by seasonal factors. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT00340132, NCT00342732.

Effects of energy loads on energy and nutrient absorption rates and gut microbiome in humans: A randomized crossover trial.

OBJECTIVE: This study aimed to determine the effects of different energy loads on the gut microbiota composition and the rates of energy and nutrient excretion via feces and urine. METHODS: A randomized crossover dietary intervention study was conducted with three dietary conditions: overfeeding (OF), control (CON), and underfeeding (UF). Ten healthy men were subjected to each condition for 8 days (4 days and 3 nights in nonlaboratory and laboratory settings each). The effects of dietary conditions on energy excretion rates via feces and urine were assessed using a bomb calorimeter. RESULTS: Short-term energy loads dynamically altered the gut microbiota at the α-diversity (Shannon index), phylum, and genus levels (p < 0.05). Energy excretion rates via urine and urine plus feces decreased under OF more than under CON (urine -0.7%; p < 0.001, urine plus feces -1.9%; p = 0.049) and UF (urine -1.0%; p < 0.001, urine plus feces -2.1%; p = 0.031). However, energy excretion rates via feces did not differ between conditions. CONCLUSIONS: Although short-term overfeeding dynamically altered the gut microbiota composition, the energy excretion rate via feces was unaffected. Energy excretion rates via urine and urine plus feces were lower under OF than under CON and UF conditions.

Dipeptidyl peptidase-4 inhibitor anagliptin facilitates restoration of dextran sulfate sodium-induced colitis.

OBJECTIVE. Inflammatory bowel disease (IBD) is a chronic debilitating disease associated with severe damage to the intestinal mucosa. Glucagon-like peptide-2 (GLP-2) is a potent and specific gastrointestinal growth factor. GLP-2 released from enteroendocrine cells is inactivated by dipeptidyl peptidase-4 (DPP-4). The aim of this study was to examine whether the DPP-4 inhibitor anagliptin improves experimental murine colitis. MATERIAL AND METHODS. Male C57BL/6 mice aged 8 weeks were exposed to 1.5% dextran sulfate sodium (DSS) in drinking water for 7 days to induce experimental colitis. Anagliptin (0.1% in diet) was administrated from 2 days before the beginning of DSS to 7 days after the end of DSS. Changes in body weight and disease activity index were evaluated daily. Histological colitis severity, cellular proliferation and gene expression were determined in colonic tissues. RESULTS. Treatment with anagliptin clearly improved body weight loss and disease activity index in the recovery phase. Histological score in the DSS + anagliptin group at day 14 was significantly lower than that in the DSS alone group. Treatment with anagliptin increased the Ki67-positive rate at days 10 and 14, and tended to increase insulin-like growth factor-1 mRNA expression in the DSS + anagliptin group. CONCLUSION. In this model of experimental colitis, the DPP-4 inhibitor anagliptin facilitated the restoration of mucosal damage, thereby resulting in the acceleration of healing. These findings suggest a new and novel therapeutic approach for the treatment of IBD.

Characterization of bacterial biota in the distal esophagus of Japanese patients with reflux esophagitis and Barrett's esophagus.

BACKGROUND: The distal esophagus harbors a complex bacterial population. We hypothesized that a better understanding of bacterial communities in the esophagus would facilitate understanding of the role of bacteria in esophageal disease. Here, we investigated bacterial composition in the distal esophagus in subjects with a normal esophagus, reflux esophagitis, and Barrett's esophagus. METHODS: Two biopsy specimens were obtained from the distal esophagus at 1 cm above the gastroesophageal junction under endoscopic examination in 18 patients (6 each with normal esophagus, reflux esophagitis, and Barrett's esophagus) and used for histological examination and DNA extraction. Fragments of 16S rDNA genes were amplified by PCR using general bacterial primers, and bacterial populations were examined. A third biopsy specimen was taken from the patients with Barrett's esophagus to histologically confirm the replacement of squamous epithelium with columnar epithelium in the distal esophagus. RESULTS: Endoscopic diagnoses of normal esophagus, esophagitis, and Barrett's esophagus were confirmed by histological findings. The total amount of bacterial DNA detected did not significantly differ among groups (p > 0.1). On average, each of the 18 subjects yielded about 350 clones, of which 40 were randomly picked and sequenced. Analysis of 147 16S rDNA sequences from 240 clones of 6 subjects with normal esophagus yielded four phyla, Proteobacteria (49%), Firmicutes (40%), Bacteroidetes (8%), and Actinobacteria (3%). Similar analysis of 139 16S rDNA sequences from 240 clones of 6 patients with reflux esophagitis yielded 6 phyla, Proteobacteria (43%), Firmicutes (33%), Bacteroidetes (10%), Fusobacteria (10%), Actinobacteria (2%), and TM7 (2%). while that of 138 16S rDNA sequences from 240 clones of 6 cases of Barrett's esophagus yielded 5 phyla, Firmicutes (55%), Proteobacteria (20%), Bacteroidetes (14%), Fusobacteria (9%), and Actinobacteria (2%). Thus, microbial communities differed among patients with a normal esophagus, reflux esophagitis and Barrett's esophagus. CONCLUSIONS: Esophageal bacterial composition differs under conditions of normal esophagus, reflux esophagitis, and Barrett's esophagus. Diverse bacterial communities may be associated with esophageal disease.

Cutting edge: tubulin α functions as an adaptor in NFAT-importin ß interaction.

Upon T cell stimulation, NFAT is dephosphorylated by calcineurin, leading to nuclear translocation via NFAT-importin ß interaction. Whereas the process of NFAT dephosphorylation has been well researched, the molecular mechanism of NFAT-importin ß interaction remains unknown. In contrast to NF-κB and STAT, no importin α family members have been reported as adaptor proteins for NFAT. Our study shows that tubulin α, but not tubulin ß, binds to the N-terminal region of NFAT containing the regulatory and Rel homology domains. Importin ß interacts with the NFAT-tubulin α complex rather than NFAT or tubulin α alone, resulting in cotranslocation of NFAT and tubulin α into the nucleus. Furthermore, the interaction is suppressed by acetate-induced tubulin α acetylation at lysine 40. In conclusion, tubulin α functions as an adaptor in NFAT-importin ß interaction, and this function is regulated by acetate-induced acetylation.