Impact of the Comprehensive Awareness Modification of Mouth, Chewing and Meal (CAMCAM) Program on the Attitude and Behavior Towards Oral Health and Eating Habits as Well as the Condition of Oral Frailty: A Pilot Study.

OBJECTIVES: Preserving sufficient oral function and maintaining aadequate nutrition are essential for preventing physical frailty and the following long-term care. We recently developed the 6-month Comprehensive Awareness Modification of Mouth, Chewing And Meal (CAMCAM) program, in which participants gather monthly to learn about oral health and nutrition while eating a textured lunch together. This study examined whether the CAMCAM program could improve attitude and behavior towards oral health, mastication, and diet as well as ameliorate oral frailty in community-dwelling older adults. DESIGN: Single-arm pre-post comparison study. SETTING AND PARTICIPANTS: A total of 271 community-dwelling adults (72.3 ± 5.7 years of age; 159 women [58.7%]) in 4 Japanese municipalities were recruited, of which 249 participants (92%) were assessed at the final evaluation. INTERVENTION: Participants gathered once a month at community centers to learn about oral health and nutrition while eating a "munchy" textured lunch containing proper nutrition. MEASUREMENTS: Oral frailty, frailty, and eating behavior were evaluated with the Oral Frailty Index-8 (OFI-8), Kihon checklist (KCL), and CAMCAM checklist, respectively. Participants were divided into Oral frailty (OF) and Robust groups according to OFI-8 scores. The differences in KCL and CAMCAM checklist results between the OF and Robust groups were statistically tested along with changes in scores after the program. RESULTS: KCL and CAMCAM checklist scores were significantly lower in the OF group at the initial assessment. OFI-8 and KCL findings were significantly improved in the OF group after completing the program (all P <0.05). Regarding the CAMCAM checklist, awareness of chewing improved significantly in the Robust group (P=0.009), with a similar tendency in the OF group (P=0.080). CONCLUSION: The findings of this pilot study suggest that the CAMCAM program may improve both oral and systemic frailty in addition to attitudes towards chewing, oral health, and meals, especially in individuals with oral frailty. The CAMCAM program merits expansion as a community-based frailty prevention program.

Poor Health Behaviors among Housebound Japanese Community-Dwelling Older Adults Due to Prolonged Self-Restraint during the First COVID-19 Pandemic: A Cross-Sectional Survey.

BACKGROUND: Prolonged self-restraining behaviors induced by the coronavirus disease 2019 (COVID-19) pandemic's containment measures can limit various positive health behaviors. OBJECTIVE: We examined the decline in going-out and certain other positive health behaviors and investigated the relationship between excessive decreases in going-out frequency and declining engagement in positive health behaviors among community-dwelling older adults during the self-restraint period. DESIGN: This study employed a cross-sectional survey design. SETTING: This study was conducted in Nishi Tokyo City, Tokyo, Japan. PARTICIPANTS: The participants were 294 respondents (150 women) aged 50 years and older who lived in public housing that were permitted to be surveyed during the self-restraint period. MEASUREMENTS: Their pre-pandemic going-out frequency around February 2020 and going-out frequency during the self-restraint period starting in April 2020 were reported. We mainly assessed the existence of home health behaviors (i.e., exercise, in-person and phone conversations, and healthy diet). A self-report questionnaire was used to obtain data. RESULTS: Going-out frequency decreased in 41.2% of the 294 respondents owing to the government's request for self-restraint. In total, 13 individuals had been going out less than one time per week (housebound) before the request. Of the 281 people who were not housebound before the government's self-restraint request, 13.9% were newly housebound. Newly housebound individuals were 5.3 times less likely to exercise, had 2.1 times fewer social contacts, and 2.6 times less balanced or healthy diets than those who maintained their frequency of going out. CONCLUSIONS: Prolonged self-restraint due to the COVID-19 pandemic may lead to housebound status and poor health behaviors. Public health intervention is needed to prevent excessive self-restraint, along with new measures integrating information and communication technologies to enable older adults to live active lives.

Testing mosses exposed in bags as biointerceptors of airborne radiocaesium after the Fukushima Dai-ichi Nuclear Power Station accident.

Eight years after the Fukushima nuclear accident, mosses exposed in bags were used to investigate their ability to accumulate radiocaesium and therefore to act as biointerceptors of 134Cs and 137Cs in the evacuated area of the Fukushima territory. Bags were filled with 3 widely studied moss species (Sphagnum palustre, Hypnum cupressiforme, and Hypnum plumaeforme) and exposed for 3, 6 or 9 weeks at 5 former residential sites within the Fukushima area and, for comparison, at three background sites located 700 km away. The radiocaesium activity concentrations found in moss bags were evaluated as function of exposure time, site conditions and moss species. In the Fukushima area, the moss bags accumulated 137Cs at all exposure sites and in all exposure periods, with S. palustre having the highest 137Cs accumulation ability. The 137Cs activity concentrations (from 28 to 4700 Bq kg-1) measured in moss bags increased with the exposure time and were consistent with the decontamination status of each exposure site, highlighting the big potential of moss bags to discriminate among exposure sites. Time dependency of 137Cs activity concentrations measured in mosses allowed the calculation of location-specific and species-specific factors, which can be used to predict radiocaesium accumulation trends in future biomonitoring surveys performed in the same area with the same experimental design. Autoradiography and electron microscopy analyses of the moss surfaces revealed a prevalence of soil-derived particulate form of radiocaesium, suggesting the use of moss bags as warning sensors of resuspended particles potentially harmful for local residents.

Social Detachment Influenced Muscle Mass and Strength during the COVID-19 Pandemic in Japanese Community-Dwelling Older Women.

Social detachment due to coronavirus disease (COVID-19) has caused a decline in physical activity, leading to sarcopenia and frailty in older adults. This study aimed to compare muscle mass, strength, and function values in older women before and after the first wave of the COVID-19 pandemic (April-May 2020). Furthermore, changes in muscle measures across women who experienced different levels of impact on their social participation due to the COVID-19 pandemic were examined. Muscle mass (total, trunk, and appendicular muscle), grip strength, oral motor skills, social interactions (social network and participation), and social support were assessed in 46 Japanese community-dwelling older women (mean, 77.5 y; range 66-93 y) before and after the first wave of the COVID-19 pandemic. Trunk muscle mass significantly decreased after the first wave of the pandemic. When comparing changed values between the enhanced/maintained and reduced group during the pandemic, significant group difference was observed in trunk muscular mass, grip strength, and oral motor skills. Intriguingly, those who enhanced social participation had a positive change of grip strength values, showing that social participation might influence muscle function during the COVID-19 pandemic.

TRENDS IN THE PREVALENCE OF FRAILTY IN JAPAN: A META-ANALYSIS FROM THE ILSA-J.

OBJECTIVE: To examine whether age-specific prevalence of frailty in Japan changed between 2012 and 2017. DESIGN: This study performed meta-analyses of data collected from 2012 to 2017 using the Integrated Longitudinal Studies on Aging in Japan (ILSA-J), a collection of representative Japanese cohort studies. SETTING: The ILSA-J studies were conducted on community-living older adults. PARTICIPANTS: ILSA-J studies were considered eligible for analysis if they assessed physical frailty status and presence of frailty in the sample. Seven studies were analyzed for 2012 (±1 year; n = 10312) and eight studies were analyzed for 2017 (±1 year; n = 7010). Five studies were analyzed for both 2012 and 2017. MEASUREMENTS: The study assessed the prevalence of frailty and frailty status according to 5 criteria: slowness, weakness, low activity, exhaustion, and weight loss. RESULTS: The overall prevalence of physical frailty was 7.0% in 2012 and 5.3% in 2017. The prevalence of frailty, especially in people 70 years and older, tended to decrease in 2017 compared to 2012. Slight decreases were found in the prevalence of frailty subitems including weight loss, slowness, exhaustion, and low activity between 2012 and 2017, but change in the prevalence of weakness was weaker than other components. CONCLUSIONS: The prevalence of physical frailty decreased from 2012 to 2017. There are age- and gender-related variations in the decrease of each component of frailty.

Association of residual gastric acid secretion with persistent symptoms in gastroesophageal reflux disease patients receiving standard-dose proton pump inhibitor therapy.

BACKGROUND: Although a third of gastroesophageal reflux disease (GERD) patients are refractory to proton pump inhibitor (PPI) therapy, the underlying mechanism of the refractoriness remains unclear. We compared the level of gastric acid suppression during PPI treatment between responders and non-responders by directly measuring gastric acid secretion in GERD patients taking PPIs. METHODS: Seventy-five consecutive patients receiving standard-dose PPI therapy for GERD were prospectively recruited, irrespective of persistent GERD symptoms. They were asked about their GERD symptoms using a validated questionnaire, and simultaneously underwent both a routine endoscopic examination and a gastric acid secretory testing using an endoscopic gastrin test. Associations between residual gastric acid secretion during PPI treatment and persistent GERD symptoms were analyzed by a logistic regression analysis. RESULTS: Overall, 26 of 75 (34.7%) patients were judged to be positive for persistent GERD symptoms. The patients with and without persistent symptoms showed similar gastric acid secretion levels (1.3 [1.3] mEq/10 min vs. 1.4 [2.0] mEq/10 min). Sufficient gastric acid suppression, defined as < 0.6, was not significantly associated with persistent GERD symptoms (odds ratio 1.1, 95% confidence interval 0.40-3.5). CONCLUSIONS: This study provided solid evidence to support that the gastric acid suppression level during PPI treatment does not differ between patients with and without persistent GERD symptoms. The insignificant role of residual gastric acid in the persistent GERD symptoms suggests that the use of medications other than those that enhance gastric acid inhibitory effects would be an essential approach for the management of PPI-refractory GERD.

Frailty Checkup Supporters' Intentions to Participate in Human-Resource Development and Training Activities.

BACKGROUND: Frailty prevention is one of social prescriptions for an aging society. That requires community level intervention. OBJECTIVES: This study examined frailty checkup supporters' (FCSs') intentions to engage in human-resource development and training activities (i.e., leadership activities) and related factors. DESIGN: Cross-sectional study. SETTING: Three municipalities in suburban area, Eastern Japan. PARTICIPANTS: Forty-five of 59 FCSs completed anonymous self-administered questionnaires. MEASUREMENTS: Questionnaire sought information regarding their sociodemographic data, their perceptions and experiences of FCS activities, and their intentions to participate in human-resource development and training activities. Participants were divided into a high intention (HI) and low intention group (LI). The two groups were compared using quantitative and qualitative data. RESULTS: Eleven FCSs reported intending to engage in leader-related activities. Factors associated with FCSs' intentions were finding FCS activities rewarding and the willingness to continue performing FCS activities. The participants who changed their daily activities (p = .041) and perceptions regarding contributing to the community (p = .018) showed significantly higher intention than LI participants. Free description about the changes in perceptions and lifestyles as a consequence of participating in FCS activities were analyzed qualitatively. FCSs who changed their daily activities and perspectives about contributing to the community described positive changes in both the groups. Meanwhile, FCSs who did not change their daily activities and perspectives about contributing to the community described their reason only in the LI group. CONCLUSIONS: The results might encourage FCSs to participate in training and guidance activities, as they have positive experiences and receive recognition obtained through participation in such activities.

Association between Traditional Japanese Diet Washoku and Sarcopenia in Community-Dwelling Older Adults: Findings from the Kashiwa Study.

OBJECTIVES: To identify the dietary patterns among community-dwelling Japanese older adults and to explore the association between these patterns and sarcopenia. DESIGN: Cross-sectional study. SETTING: Kashiwa city, Chiba prefecture, Japan. PARTICIPANTS: Community-dwelling older adults (n = 1241) aged 65 years and over who were not eligible for long-term care. MEASUREMENTS: Dietary intake was assessed using the brief self-administered diet history questionnaire (BDHQ). Dietary patterns were identified using both principal component analysis and the score on the Japanese diet comprising soybeans and soybean products, fish, vegetables, pickles, mushroom, seaweeds, and fruits. Sarcopenia was defined by the Asian Working Group for Sarcopenia (AWGS) criteria. A binary logistic regression analysis was performed with sarcopenia status as the dependent variable after adjusting for economic status, living alone status, BMI, energy intake, multimorbidity, and physical activity. RESULTS: Participants' mean age was 74.6 years, and 52.1% were male. According to AWGS criteria, 5.1% had sarcopenia. Three dietary patterns were identified from the principal component analysis. Dietary pattern 1 (DP1), showed high loadings for fish, tofu, vegetables, and fruits which are similar to the side dishes in a typical Japanese diet. Dietary pattern 2 (DP2) had high factor loadings for fish, rice, and miso soup which are main dishes in a typical Japanese diet. Dietary pattern 3 (DP3) had a high factor loading for noodles. Men with the lowest tertile of DP1 score had a higher likelihood of being sarcopenic (Adjusted odds ratio (AOR) 3.67, 95% confidence interval (CI) 1.20-11.2). Women with the lowest tertile of DP2 score had a moderate likelihood of being sarcopenic (AOR 2.71, 95%CI 0.99-7.46). Low adherence to Japanese dietary pattern was associated with prevalence of sarcopenia in both genders. CONCLUSION: Adherence to a dietary pattern high in foods characteristic of a Japanese diet including fish, soybean products, vegetables, and fruits was associated with low prevalence of sarcopenia in both genders.

Living with Family yet Eating Alone is Associated with Frailty in Community-Dwelling Older Adults: The Kashiwa Study.

OBJECTIVES: Eating alone is related to depression, nutritional risk, and mortality. These effects are also influenced by living status. However, little is known about the relationship between eating alone despite living with family and frailty. This study explores the relationship of eating alone and living status with frailty in community-dwelling older adults. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Kashiwa city, Chiba prefecture, Japan; randomly selected community-dwelling older adults (aged 65 years and over). MEASUREMENTS: Eating status was assessed by the question, "Do you eat meals with anyone, at least once a day: yes or no?" Frailty was defined by Kihon Checklist (KCL) score 8 or over. Domains of frailty were divided into instrumental activities of daily living (IADL), physical strength, nutrition, eating, socialization, memory, and mood, based on KCL categories. Binary logistic regression analysis was used, adjusting for age, years of education, chronic diseases, number of teeth and cognitive function. RESULTS: Among the total of 1,914 participants, 49.8% were male, and the overall mean age was 72.9 ± 5.5 years. Of all participants, 56 (5.9%) of men and 112 (11.7%) of women were frail. Older adults who ate alone despite living with others were more likely to be frail (OR 2.49, 95%CI 1.1-5.5 for men and OR 2.16, 95%CI 1.0-4.5 for women). Of particular note, eating and living status were associated with lower physical strength and mood in men, whereas in women these statuses were associated with lower scores for IADL, socialization, memory, and mood. CONCLUSIONS: Eating alone despite living with others was associated with high frailty in both genders; however, the pathways were different between genders. These results might help yield a simple, fundamental intervention approach to multifaceted frailty, reflecting gender and associated high-risk domains.

Radiologic and Pathologic Features of the Transmantle Sign in Focal Cortical Dysplasia: The T1 Signal Is Useful for Differentiating Subtypes.

BACKGROUND AND PURPOSE: The transmantle sign is a characteristic MR imaging finding often seen in focal cortical dysplasia type IIb. The transmantle sign is typically hyperintense on T2WI and FLAIR and hypointense on T1WI. However, in some cases, it shows T1 high signal. We evaluated the imaging and pathologic findings to identify the causes of the T1 high signal in the transmantle sign. MATERIALS AND METHODS: We retrospectively reviewed the preoperative imaging data of 141 consecutive patients with histologically proved focal cortical dysplasia. We selected 25 patients with focal cortical dysplasia with the transmantle sign and divided them into groups based on the pathologic focal cortical dysplasia subtype and T1 signal of the transmantle sign. We evaluated the clinical, radiologic, and pathologic findings, including the number of balloon cells and dysmorphic neurons and the severity of gliosis or calcifications and compared them among the groups. RESULTS: Nine of the 25 patients had a T1-high-signal transmantle sign; the other 16 patients did not. All 9 patients with a T1-high-signal transmantle sign were diagnosed as type IIb (group A). Of the 16 patients with no T1-high-signal transmantle sign, 13 were diagnosed as having type IIb (group B), and the other 3 patients, as type IIa (group C). The number of balloon cells was significantly higher in group A than in the other groups, but there were no differences regarding dysmorphic neurons, the severity of gliosis, or calcifications. CONCLUSIONS: Approximately 6% (9/141) of this patient series had a T1-high-signal transmantle sign, and all were type IIb. The signal may reflect a rich density of balloon cells. This finding could support the differentiation of subtypes, especially type IIb.

Oxidative stress serves as a key checkpoint for IL-33 release by airway epithelium.

BACKGROUND: Interleukin (IL)-33 is implicated in the pathophysiology of asthma and allergic diseases. However, our knowledge is limited regarding how IL-33 release is controlled. The transcription factor nuclear factor-erythroid-2-related factor 2 (Nrf2) plays a key role in antioxidant response regulation. OBJECTIVE: The goal of this project was to investigate the role of cellular oxidative stress in controlling IL-33 release in airway epithelium. METHODS: Complementary approaches were used that included human bronchial epithelial cells and mouse models of airway type-2 immunity that were exposed to fungus Alternaria extract. The clinically available Nrf2 activator 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid methyl ester (CDDO-Me) was used to evaluate the role of Nrf2-induced antioxidant molecules. RESULTS: Human bronchial epithelial cells produced reactive oxygen species (ROS) when they were exposed to Alternaria extract. ROS scavengers, such as glutathione (GSH) and N-acetyl cysteine, prevented extracellular secretion of ATP and increases in intracellular calcium concentrations that precede IL-33 release. Administration of CDDO-Me to mice enhanced expression of a number of antioxidant molecules in the lungs and elevated lung levels of endogenous GSH. Importantly, CDDO-Me treatment reduced allergen-induced ATP secretion and IL-33 release by airway epithelial cells in vitro and protected mice from IL-33 release and asthma-like pathological changes in the lungs. CONCLUSIONS: The balance between oxidative stress and antioxidant responses plays a key role in controlling IL-33 release in airway epithelium. The therapeutic potential of Nrf2 activators needs to be considered for asthma and allergic airway diseases.

IL-33 mediates reactive eosinophilopoiesis in response to airborne allergen exposure.

BACKGROUND: Exposure to aeroallergens induces eosinophilic airway inflammation in patients with asthma and allergic airway diseases. The circulating number of eosinophils in peripheral blood is relatively small, leading us to hypothesize that bone marrow needs to be engaged quickly to meet the demands of the tissues. METHODS: To investigate the communication between the lungs and bone marrow, we used acute allergen exposure and airway inflammation models in mice. Gene-deficient mice and cytokine reporter mice as well as in vitro cell culture models were used to dissect the mechanisms. RESULTS: Naïve BALB/c mice produced increased numbers of eosinophil precursors and mature eosinophils in the bone marrow when their airways were exposed to a common fungal allergen, Alternaria alternata. Expression of IL-5 and IL-33 increased rapidly in the lungs, but not in the bone marrow. Sera from allergen-exposed mice promoted eosinophilopoiesis in bone marrow cells from naïve mice, which was blocked by anti-IL-5 antibody. Mice deficient in the IL-33 receptor ST2 (i.e., Il1rl1(-/-) mice) were unable to increase their serum levels of IL-5 and allergen-induced eosinophilopoiesis in the bone marrow after allergen exposure. Finally, group 2 innate lymphoid cells (ILC2s) in the lungs showed robust expression of IL-5 after Alternaria exposure. CONCLUSIONS: These finding suggests that lung IL-33, through innate activation of ILC2s and their production of IL-5, plays a key role in promoting acute reactive eosinophilopoiesis in the bone marrow when naïve animals are exposed to airborne allergens. Therefore, bone marrow eosinophilopoiesis may be affected by atmospheric environmental conditions.

Screening for Malnutrition in Community Dwelling Older Japanese: Preliminary Development and Evaluation of the Japanese Nutritional Risk Screening Tool (NRST).

BACKGROUND: Early and effective screening for age-related malnutrition is an essential part of providing optimal nutritional care to older populations. OBJECTIVE: This study was performed to evaluate the adaptation of the original SCREEN II questionnaire (Seniors in the Community: Risk Evaluation for Eating and Nutrition, version II) for use in Japan by examining its measurement properties and ability to predict nutritional risk and sarcopenia in community-dwelling older Japanese people. The ultimate objective of this preliminary validation study is to develop a license granted full Japanese version of the SCREEN II. PARTICIPANTS: The measurement properties and predictive validity of the NRST were examined in this cross-sectional study of 1921 community-dwelling older Japanese people. MEASUREMENTS: Assessments included medical history, and anthropometric and serum albumin measurements. Questions on dietary habits that corresponded to the original SCREEN II were applied to Nutritional Risk Screening Tool (NRST) scoring system. Nutritional risk was assessed by the Geriatric Nutrition Risk Index (GNRI) and the short form of the Mini-Nutritional Assessment (MNA-SF). Sarcopenia was diagnosed according to the criteria of the European Working Group on Sarcopenia in Older People. RESULTS: The nutritional risk prevalences determined by the GNRI and MNA-SF were 5.6% and 34.7%, respectively. The prevalence of sarcopenia was 13.3%. Mean NRST scores were significantly lower in the nutritionally at-risk than in the well-nourished groups. Concurrent validity analysis showed significant correlations between NRST scores and both nutritional risk parameters (GNRI or MNA-SF) and sarcopenia. The areas under the receiver operating characteristic curves (AUC) of NRST for the prediction of nutritional risk were 0.635 and 0.584 as assessed by GNRI and MNA-SF, respectively. AUCs for the prediction of sarcopenia were 0.602 (NRST), 0.655 (age-integrated NRST), and 0.676 (age and BMI-integrated NRST). CONCLUSIONS: These results indicate that the NRST is a promising screening tool for the prediction of malnutrition and sarcopenia in community-dwelling older Japanese people. Further development of a full Japanese version of the SCREEN II is indicated.

Changes in tumor expression of HER2 and hormone receptors status after neoadjuvant chemotherapy in 21,755 patients from the Japanese breast cancer registry.

BACKGROUND: We investigate rates of pathologic complete response (pCR) and tumor expression of ER, PgR, HER2 discordance after neoadjuvant chemotherapy using Japanese breast cancer registry data. PATIENTS AND METHODS: Records of more than 300,000 breast cancer cases treated at 800 hospitals from 2004 to 2013 were retrieved from the breast cancer registry. After data cleanup, we included 21,755 patients who received neoadjuvant chemotherapy and had no distant metastases. pCR was defined as no invasive tumor in the breast detected during surgery after neoadjuvant chemotherapy. HER2 overexpression was determined immunohistochemically and/or using fluorescence in situ hybridization. RESULTS: pCR was achieved in 5.7% of luminal tumors (n = 8730), 24.6% of HER2-positive tumors (n = 4403), and 18.9% of triple-negative tumors (n = 3660). Among HER2-positive tumors, pCR was achieved in 31.6% of ER-negative tumors (n = 2252), 17.0% of ER-positive ones (n = 2132), 31.4% of patients who received trastuzumab as neoadjuvant chemotherapy (n = 2437), and 16.2% of patients who did not receive trastuzumab (n = 1966). Of the 2811 patients who were HER2-positive before treatment, 601 (21.4%) had HER2-negative tumors after neoadjuvant chemotherapy, whereas 340 (3.4%) of the 9947 patients with HER2-negative tumors before treatment had HER2-positive tumors afterward. Of the 10,973 patients with ER-positive tumors before treatment, 499 (4.6%) had ER-negative tumors after neoadjuvant chemotherapy, whereas 519 (9.3%) of the 5607 patients who were ER-negative before treatment had ER-positive tumors afterward. CONCLUSION: We confirmed that loss of HER2-positive status can occur after neoadjuvant treatment in patients with primary HER2-positive breast cancer. We also confirmed that in practice, differences in pCR rates between breast cancer subtypes are the same as in clinical trials. Our data strongly support the need for retest ER, PgR, HER2 of surgical sample after neoadjuvant therapy in order to accurately determine appropriate use of targeted therapy.

Basophil infiltration in eosinophilic oesophagitis and proton pump inhibitor-responsive oesophageal eosinophilia.

BACKGROUND: The features of proton pump inhibitor-responsive oesophageal eosinophilia (PPI-REE) are similar to those of eosinophilic oesophagitis (EoE), but PPI-REE demonstrates symptomatic and histological responses to PPI therapy. Several studies have shown that basophils play a crucial role in the pathogenesis of allergic diseases. AIM: To identify and compare basophil infiltration in the oesophageal epithelium in patients with EoE, PPI-REE, gastroesophageal reflux disease (GERD) and normal oesophagus (controls). METHODS: Biopsy specimens from 43 patients, including 12 with EoE, 11 with PPI-REE, 10 with GERD and 10 normal oesophagus, were analysed. Immunohistochemistry was performed to quantify the number of basophils and mast cells in the oesophageal epithelium. Double immunofluorescence staining for thymic stromal lymphopoietin (TSLP) and basophils was performed. Patients with EoE were treated with swallowed fluticasone. RESULTS: There were no differences in clinical, endoscopic or histological features between patients with EoE and PPI-REE. There were more basophils and mast cells in patients with EoE and PPI-REE than in patients with GERD and control subjects. Basophil infiltration of the oesophageal epithelium in patients with EoE was higher than that in patients with PPI-REE (3.6 ± 2.8 per high power field vs. 1.2 ± 0.9 per high power field respectively; P = 0.02); however, there was no significant difference in mast cell infiltration between the two groups. TSLP was highly expressed in the oesophageal epithelium in areas infiltrated by basophils. Steroid therapy significantly decreased intraepithelial basophils in patients with EoE. CONCLUSION: Basophils may play an important role in the pathogenesis of eosinophilic oesophagitis.

Identification of a high-risk group for low-dose aspirin-induced gastropathy by measuring serum pepsinogen in H. pylori-infected subjects.

BACKGROUND: We recently demonstrated in humans that the extent of low-dose aspirin (LDA)-induced gastropathy was directly related to the individual gastric acid secretion level. We also established reliable cutoff serum pepsinogen (PG) values to predict gastric acid secretion status. In this study, we investigated the clinical usefulness of measuring the serum pepsinogen values for identifying a high-risk group for gastric mucosal injury among chronic LDA users. METHODS: One hundred long-term LDA users were enrolled in this analysis. Serum from each subject was subjected to determination of H. pylori status and measurement of pepsinogen values. According to our recent report, a PG I value ≥ 50 ng/mL was defined as estimated hyperchlorhydria in H. pylori-negative subjects, while a PG I/II ≥ 3.3 was defined as estimated hyperchlorhydria in H. pylori-positive subjects. The grade of gastric mucosal injury was assessed endoscopically, and multiple logistic regression analyses were used to estimate the risk. RESULTS: Estimated hyperchlorhydria was a strong independent risk for intensive gastric mucosal injury with an OR (95% CI): 34.0 (4.5-259) and for gastric ulcer with an OR (95% CI): 10.2 (1.8-58.3) in H. pylori-positive subjects, while it was not a significant risk in H. pylori-negative subjects. The association persisted even after excluding those with conventional risks for LDA-gastropathy such as ulcer histories. CONCLUSION: Using simple serum measurement of H. pylori antibody and pepsinogen concentrations, an extremely high-risk group for LDA-induced gastropathy could be extracted, and these patients should become a therapeutic target for prevention of LDA-induced gastropathy.

Group 2 innate lymphoid cells and CD4+ T cells cooperate to mediate type 2 immune response in mice.

BACKGROUND: Innate lymphoid cells (ILCs) play important roles in innate immunity and tissue remodeling via production of various cytokines and growth factors. Group 2 ILCs (ILC2s) were recently shown to mediate the immune pathology of asthma even without adaptive immunity. However, little is known about possible interactions between ILC2s and other immune cells. We sought to investigate the capacity of ILC2s to regulate effector functions of T cells. METHODS: We isolated ILC2s from the lungs of naïve mice. We cultured CD4(+) T cells with ILC2s in vitro and examined the functions of these cell types. The mechanisms were investigated using blocking antibodies and cells isolated from cytokine-deficient mice. For the in vivo study, we adoptively transferred ILC2s and CD4(+) T cells into Il7ra(-/-) mice and subsequently exposed the mice to ovalbumin and a cysteine protease. RESULTS: Lung ILC2s enhanced CD4(+) T-cell proliferation and promoted production of type 2 cytokines in vitro. The interaction between ILC2s and CD4(+) T cells involved costimulatory molecule OX40L and cytokine IL-4, which was mainly derived from ILC2s. Adoptive transfer of both ILC2 and CD4(+) T-cell populations, but not each population alone, into Il7ra(-/-) mice resulted in induction of a robust antigen-specific type 2 cytokine response and airway inflammation. CONCLUSION: Lung ILC2s function to promote adaptive immunity in addition to their established roles in innate immunity. This novel function of ILC2s needs to be taken into account when considering the pathophysiology of asthma and other allergic airway diseases.

Reactive increase in gastric mucus secretion is an adaptive defense mechanism against low-dose aspirin-induced gastropathy.

BACKGROUND: Gastric mucus is considered to play an essential role in gastric mucosal defense mechanisms, especially when irritants are present in the stomach. AIM: To investigate the relationship between low-dose aspirin-induced gastropathy and gastric secretory function, especially gastric mucus secretion, in healthy volunteers. METHODS: Thirty male, asymptomatic, Helicobacter pylori pylori-negative healthy volunteers were asked to take 100 mg of enteric-coated aspirin (Bayaspirin) once a day for 10 days. Endoscopic examination was performed before and 3 and 10 days after drug administration. The extent of endoscopically assessed gastric mucosal injury was semi-quantitatively evaluated according to the modified Lanza score. The pentagastrin-stimulated gastric juice was collected for 10 min during the endoscopic examination and subjected to analysis for gastric acid (mEq/10 min) or mucus (mg hexose/10 min) output. RESULTS: Overall, the 10-day aspirin treatment significantly increased gastric mucus secretion from 0.8 (interquartile range 1.7) to 1.6 (1.6) mg hexose/10 min (P < 0.05), with a concomitant and significant decrease in the gastric acid/mucus ratio from 4.3 (5.2) to 2.9 (4.7) (P < 0.01). Subsequent analysis of two subgroups of volunteers categorized according to their endoscopic status ("severe gastropathy" vs. "modest gastropathy") revealed that changes in gastric secretory parameters occurred exclusively in those subjects without severe gastric injury; there was no alteration in these parameters in subjects with severe gastric injury. CONCLUSIONS: The results of this study suggest that the reactive increase in gastric mucus secretion is an adaptive defense mechanism against low-dose aspirin-induced gastropathy. In some individuals, such a response may be insufficient to prevent the development of severe mucosal injury and even ulcers and their complications.

Impact of pre-emptive contact precautions for outborn neonates on the incidence of healthcare-associated meticillin-resistant Staphylococcus aureus transmission in a Japanese neonatal intensive care unit.

BACKGROUND: The neonatal intensive care unit (NICU) is a high-risk setting for transmission of meticillin-resistant Staphylococcus aureus (MRSA). Very few studies have investigated the impact of pre-emptive contact precautions applied to outborn neonates transferred to an NICU on the incidence of healthcare-associated (HA)-MRSA transmission. AIM: To assess the efficacy of pre-emptive contact precautions for outborn neonates implemented in an NICU. METHODS: A before-and-after intervention study was conducted in the NICU of Kobe University Hospital. Pre-emptive contact precautions for outborn neonates were introduced in September 2008. The period before the introduction of pre-emptive contact precautions (January 2007-August 2008) was compared with the period after the introduction of pre-emptive contact precautions (September 2008-December 2010). Data for all admitted neonates, neonates who stayed in the NICU for more than three days, length of NICU stay, incidence of MRSA-positive outborn neonates on admission, hand hygiene compliance and incidence of HA-MRSA transmission were compared between the two periods. FINDINGS: There were no significant differences in the percentage of outborn patients admitted to the NICU, percentage of patients who stayed in the NICU for more than three days, length of NICU stay, and incidence of MRSA-positive outborn patients at NICU admission between the groups enrolled before and after the introduction of pre-emptive contact precautions. However, hand hygiene compliance increased, and the incidence of HA-MRSA transmission reduced significantly from 3.5/1000 to 1.3/1000 patient-days after the introduction of pre-emptive contact precautions (P < 0.0001). CONCLUSION: Pre-emptive contact precautions for outborn neonates were effective in reducing the incidence of HA-MRSA transmission in a Japanese NICU.